Chronic hepatitis C and no response to antiviral therapy: potential current and future therapeutic options.

Abstract:

:A significant proportion of chronic hepatitis C patients fails to achieve sustained virologic response even after treatment with the current, more potent, combination of pegylated interferon-alpha (IFNa) plus ribavirin. Such patients represent a rather heterogeneous group and may be divided initially into relapsers and nonresponders. Both the type of previous therapy and of previous response are very important factors for the indication and the type of re-treatment. The combination of pegylated IFNa and ribavirin seems to be a rational approach for patients who failed to respond to IFNa monotherapy. Pegylated IFNa-based regimens appear to induce sustained responses in 40-68% of relapsers but in only 11% of nonresponders to previous therapy with standard IFNa plus ribavirin. Thus, new therapeutic approaches are needed for the latter subgroup of patients as well as those who fail to respond to pegylated IFNa-based regimens. Such new approaches currently under evaluation include the triple combination of pegylated IFNa, ribavirin, and amantadine, alternative types of IFN, use of agents with ribavirin like activity but lesser degrees of side-effects, inhibitors of hepatitis C virus (HCV) replication, mainly inhibitors of NS3 protease or helicase, antisense oligonucleotides, and ribozymes, and several immunomodulators. Moreover, maintenance antifibrotic therapy, mostly with low doses of pegylated IFNa, are under evaluation in patients with advanced fibrosis. Thus, even in the current era of the potent pegylated IFNa-based regimens, the management of these difficult-to-treat patients represents an increasingly frequent problem and perhaps the most challenging therapeutic task in chronic hepatitis C.

journal_name

J Viral Hepat

authors

Papatheodoridis GV,Cholongitas E

doi

10.1111/j.1365-2893.2004.00522.x

subject

Has Abstract

pub_date

2004-07-01 00:00:00

pages

287-96

issue

4

eissn

1352-0504

issn

1365-2893

pii

JVH522

journal_volume

11

pub_type

杂志文章,评审
  • The role of the hepatitis viruses in cholangiocarcinoma.

    abstract::Cholangiocarcinoma is the second most common liver cancer in the world. The aetiology of the disease is diverse incorporating a variety of conditions leading to biliary stasis, biliary and liver inflammation, but a large number of cases still occur in the absence of established risk factors. Its incidence and mortalit...

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章,评审

    doi:10.1111/jvh.12093

    authors: Ralphs S,Khan SA

    更新日期:2013-05-01 00:00:00

  • Fibrosis staging in chronic hepatitis C: analysis of discordance between transient elastography and liver biopsy.

    abstract::In chronic hepatitis C, transient elastography (TE) accurately identifies cirrhosis, but its ability to assess significant fibrosis (Metavir > or = F2) is variable. Constitutional and liver disease-related factors may influence TE and here we examined the variables associated with differences. Three hundred consecutiv...

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章

    doi:10.1111/j.1365-2893.2009.01199.x

    authors: Calvaruso V,Cammà C,Di Marco V,Maimone S,Bronte F,Enea M,Dardanoni V,Manousou P,Pleguezuelo M,Xirouchakis E,Attanasio M,Dusheiko G,Burroughs AK,Craxì A

    更新日期:2010-07-01 00:00:00

  • Prevalence and factors associated with significant liver fibrosis assessed by transient elastometry in HIV/hepatitis C virus-coinfected patients.

    abstract::Transient elastometry (TE) could provide a more accurate evaluation of the frequency and risk factors of liver fibrosis in hepatitis C virus (HCV) infection than that based on biopsy. The aim of this study was to assess the prevalence of and factors associated with significant liver fibrosis in a large population of H...

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章,多中心研究

    doi:10.1111/j.1365-2893.2009.01229.x

    authors: Pineda JA,González J,Ortega E,Tural C,Macías J,Griffa L,Burgos A,Grafihco Study Team.

    更新日期:2010-10-01 00:00:00

  • Cytotoxic CD4 T cells in viral hepatitis.

    abstract::CD4+ T cells are thought to contribute to antiviral immune responses by secretion of cytokines thereby providing help to CD8+ T and B cells. However, perforin-positive cytotoxic CD4+ T cells have been described in human immunodeficiency virus-positive patients suggesting a role not only of CD8+ but also of CD4+ T cell...

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章

    doi:10.1111/j.1365-2893.2006.00723.x

    authors: Aslan N,Yurdaydin C,Wiegand J,Greten T,Ciner A,Meyer MF,Heiken H,Kuhlmann B,Kaiser T,Bozkaya H,Tillmann HL,Bozdayi AM,Manns MP,Wedemeyer H

    更新日期:2006-08-01 00:00:00

  • Suppression of hepatitis C virus by the flavonoid quercetin is mediated by inhibition of NS3 protease activity.

    abstract::Phytochemicals exert antiviral activity and may play a potential therapeutic role in hepatitis C virus (HCV) infection. In this work, we aimed to isolate NS3 inhibitors from traditional Indian medicinal plants that were found, in our earlier study, to inhibit HCV NS3 protease activity and to evaluate their potential t...

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章

    doi:10.1111/j.1365-2893.2011.01507.x

    authors: Bachmetov L,Gal-Tanamy M,Shapira A,Vorobeychik M,Giterman-Galam T,Sathiyamoorthy P,Golan-Goldhirsh A,Benhar I,Tur-Kaspa R,Zemel R

    更新日期:2012-02-01 00:00:00

  • Early steep decline of liver stiffness predicts histological reversal of fibrosis in chronic hepatitis B patients treated with entecavir.

    abstract::It is unknown whether dynamic changes of liver stiffness measurement (LSM) can predict the reversibility of fibrosis. Therefore, we evaluated the utility of LSM changes in predicting histological changes of fibrosis in patients with chronic hepatitis B (CHB) on antiviral therapy. In a prospective cohort of CHB patient...

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章

    doi:10.1111/jvh.13058

    authors: Kong Y,Sun Y,Zhou J,Wu X,Chen Y,Piao H,Lu L,Ding H,Nan Y,Jiang W,Xu Y,Xie W,Li H,Feng B,Shi G,Chen G,Li H,Zheng H,Cheng J,Wang T,Liu H,Lv F,Shao C,Mao Y,Sun J,Chen T,Han T,Han Y,Wang L,Ou X,Zha

    更新日期:2019-05-01 00:00:00

  • Clinical predictors of response to recombinant interferon-alpha treatment in patients with chronic non-A, non-B hepatitis (hepatitis C). The Hepatitis Interventional Therapy Group.

    abstract::Chronic non-A, non-B hepatitis (NANBH) is a common and often progressive liver disease. Based on current serological tests, hepatitis C virus (HCV) infection is responsible for most cases. Interferon-alpha (IFN) treatment at a dose of 3 x 10(6) units given three times per week for 24 weeks has been shown to be effecti...

    journal_title:Journal of viral hepatitis

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:10.1111/j.1365-2893.1994.tb00062.x

    authors: Davis GL,Lindsay K,Albrecht J,Bodenheimer HC Jr,Balart LA,Perrillo RP,Dienstag JL,Tamburro C,Schiff ER,Carey W

    更新日期:1994-01-01 00:00:00

  • The present and future disease burden of hepatitis C virus (HCV) infections with today's treatment paradigm - volume 2.

    abstract::Morbidity and mortality attributable to chronic hepatitis C virus (HCV) infection are increasing in many countries as the infected population ages. Models were developed for 15 countries to quantify and characterize the viremic population, as well as estimate the number of new infections and HCV related deaths from 20...

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章

    doi:10.1111/jvh.12351

    authors: Hatzakis A,Chulanov V,Gadano AC,Bergin C,Ben-Ari Z,Mossong J,Schréter I,Baatarkhuu O,Acharya S,Aho I,Anand AC,Andersson MI,Arendt V,Arkkila P,Barclay K,Bessone F,Blach S,Blokhina N,Brunton CR,Choudhuri G,Cisneros

    更新日期:2015-01-01 00:00:00

  • TyG index, HOMA score and viral load in patients with chronic hepatitis C due to genotype 1.

    abstract::The triglycerides × glucose (TyG) index is a recently proposed surrogate marker of insulin resistance (IR), calculated from fasting plasma triglyceride and glucose concentrations. We tested the host and viral factors associated with Tyg and homeostasis model assessment (HOMA) scores, comparing their associations with ...

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章

    doi:10.1111/j.1365-2893.2011.01439.x

    authors: Petta S,Di Marco V,Di Stefano R,Cabibi D,Cammà C,Marchesini G,Craxì A

    更新日期:2011-07-01 00:00:00

  • Role of nitric oxide synthase genes in hepatitis E virus infection.

    abstract::Hepatitis E virus (HEV) is the most common cause of endemic and epidemic acute hepatitis. A correlation between iNOS, eNOS polymorphisms, levels and severity of disease has been reported, and here, we examined the role of iNOS and eNOS gene polymorphisms and their levels in HEV-related acute viral hepatitis and acute ...

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章

    doi:10.1111/jvh.12186

    authors: Hazam RK,Deka M,Kar P

    更新日期:2014-01-01 00:00:00

  • Claudin-1, miR-122 and apolipoprotein E transductions improve the permissivity of SNU-182, SNU-398 and SNU-449 hepatoma cells to hepatitis C virus.

    abstract::Hepatitis C virus (HCV) is a human hepatotropic virus, but many hepatoma cell lines are not permissive to this virus. In a previous study, we observed that SNU-182, SNU-398 and SNU-449 hepatoma cell lines were nonpermissive to HCV. To understand the nonpermissivity, we evaluated the ability of each cell line to suppor...

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章

    doi:10.1111/jvh.12767

    authors: Fournier C,Hoffmann TW,Morel V,Descamps V,Dubuisson J,Brochot E,Francois C,Duverlie G,Castelain S,Helle F

    更新日期:2018-01-01 00:00:00

  • Change in injecting behaviour among people treated for hepatitis C virus: The role of intimate partnerships.

    abstract::Injecting behaviour in people who inject drugs is the main risk factor for hepatitis C virus (HCV) infection. Psychosocial factors such as having a partner who injects drugs and living with other drug users have been associated with increases in injecting risk behaviour. This study aimed to investigate changes in inje...

    journal_title:Journal of viral hepatitis

    pub_type: 临床试验,杂志文章

    doi:10.1111/jvh.13009

    authors: Malaguti A,Sani F,Stephens BP,Ahmad F,Dugard P,Dillon JF,ERADICATE-C Study Group.

    更新日期:2019-01-01 00:00:00

  • Drug use and phylogenetic clustering of hepatitis C virus infection among people who use drugs in Vancouver, Canada: A latent class analysis approach.

    abstract::This study estimated latent classes (ie, unobserved subgroups in a population) of people who use drugs in Vancouver, Canada, and examined how these classes relate to phylogenetic clustering of hepatitis C virus (HCV) infection. HCV antibody-positive people who use drugs from two cohorts in Vancouver, Canada (1996-2012...

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章

    doi:10.1111/jvh.12758

    authors: Jacka B,Bray BC,Applegate TL,Marshall BDL,Lima VD,Hayashi K,DeBeck K,Raghwani J,Harrigan PR,Krajden M,Montaner JSG,Grebely J Senior

    更新日期:2018-01-01 00:00:00

  • Re-treatment for severe hepatitis flare in HBeAg-negative chronic hepatitis B: An appraisal with combined HBsAg/ALT kinetics.

    abstract::To test the concept that off-therapy hepatitis flares with increasing qHBsAg require immediate re-treatment whereas re-treatment can be held or not necessary for those with decreasing qHBsAg, pre-retreatment combined HBsAg/ALT kinetics were classified in 22 patients with severe hepatitis flare (ALT > 30X ULN) and chec...

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章

    doi:10.1111/jvh.13253

    authors: Chien RN,Liaw YF

    更新日期:2020-05-01 00:00:00

  • High levels of p53 protein expression do not correlate with p53 mutations in hepatocellular carcinoma.

    abstract::To determine the relationship between p53 altered expression and p53 mutations in hepatocellular carcinoma (HCC), we analysed p53 protein immunohistochemically and assessed the presence of mutations in exons 4-8 of the p53 gene using SSCP assay in 117 HCCs corresponding to 78 patients. We also determined the relations...

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章

    doi:10.1111/j.1365-2893.2004.00541.x

    authors: Anzola M,Saiz A,Cuevas N,Lopez-Martinez M,Martinez de Pancorbo MA,Burgos JJ

    更新日期:2004-11-01 00:00:00

  • Semiquantitative assessment of IgM antibody to hepatitis B core antigen and prediction of the severity of chronic hepatitis B.

    abstract::Controversial results have been reported concerning the correlation between serum levels of IgM antibodies to hepatitis B core antigen (IgM HBcAb) and the histological activity of chronic hepatitis B. In this study, paired serum samples and liver biopsies were collected from 200 consecutive chronic hepatitis B patient...

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章

    doi:10.1046/j.1365-2893.1999.00171.x

    authors: Colloredo G,Bellati G,Sonzogni A,Zavaglia C,Fracassetti O,Leandro G,Ghislandi R,Minola E,Ideo G

    更新日期:1999-11-01 00:00:00

  • The association of HIV viral load with indirect markers of liver injury.

    abstract::This study assessed the association of HIV RNA with indirect markers of liver injury including FIB-4 index, liver enzymes and platelet counts in a high-risk Hispanic population. The data were derived from a prospective study that included 138 HIV/hepatitis C (HCV)-coinfected and 68 HIV-infected participants without he...

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章

    doi:10.1111/j.1365-2893.2011.01529.x

    authors: Forrester JE,Rhee MS,McGovern BH,Sterling RK,Knox TA,Terrin N

    更新日期:2012-02-01 00:00:00

  • Predictive value of aminotransferase and hepatitis B virus DNA levels on response to interferon therapy for chronic hepatitis B.

    abstract::In a previously reported randomized controlled trial of interferon-alpha (IFN-alpha) for chronic hepatitis B, we found a significant difference in response between Chinese adults with elevated vs normal pretreatment aminotransferase (ALT) levels. The aim of this study was to determine the correlation between serum hep...

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章

    doi:10.1046/j.1365-2893.1998.00098.x

    authors: Lok AS,Ghany MG,Watson G,Ayola B

    更新日期:1998-05-01 00:00:00

  • Study on the function of circulating plasmacytoid dendritic cells in the immunoactive phase of patients with chronic genotype B and C HBV infection.

    abstract::Hepatitis B virus (HBV) infection induces a wide range of chronic liver injury. The mechanism by which HBV evades the immune surveillance system remains obscure. Plasmacytoid dendritic cells (pDCs) seem to be the major endogenous interferon (IFN)-alpha producers and represent one of the most important cell types in th...

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章

    doi:10.1111/j.1365-2893.2006.00819.x

    authors: Wang K,Fan X,Fan Y,Wang B,Han L,Hou Y

    更新日期:2007-04-01 00:00:00

  • Estimating paediatric hepatitis C prevalence in the United States.

    abstract::Over 70 million individuals are infected with hepatitis C virus (HCV) worldwide. Yet most prevalence data are in the adult population, with little focus on paediatrics, partially due to the scarcity of public data. The objective of this paper is to examine HCV prevalence in children by estimating prevalence rates amon...

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章

    doi:10.1111/jvh.13377

    authors: Rahal H,Boutros S,Farhat M,Kullar R,Rahal K,Saab S

    更新日期:2020-12-01 00:00:00

  • Modelling hepatitis C virus kinetics during treatment with pegylated interferon alpha-2b: errors in the estimation of viral kinetic parameters.

    abstract::Neumann et al. [1] developed a widely used model for the analysis of hepatitis C virus (HCV) dynamics after the initiation of interferon therapy that assumes the effectiveness of therapy in blocking virion production, epsilon, is constant. However, with pegylated interferon alpha-2b (PEG-IFN) given weekly, there are s...

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章

    doi:10.1111/j.1365-2893.2007.00954.x

    authors: Shudo E,Ribeiro RM,Perelson AS

    更新日期:2008-05-01 00:00:00

  • BMI, male sex and IL28B genotype associated with persistently high hepatitis C virus RNA levels among chronically infected drug users up to 23 years following seroconversion.

    abstract::The natural course of serum HCV RNA levels during chronic infection remains unclear. We investigated HCV RNA levels and factors associated with HCV RNA levels for the entire course from HCV seroconversion. We measured HCV RNA levels of 54 HCV seroconverters from the Amsterdam Cohort Studies among drug users at yearly ...

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章

    doi:10.1111/jvh.12303

    authors: Grady BP,Prins M,Rebers S,Molenkamp R,Geskus RB,Schinkel J

    更新日期:2015-03-01 00:00:00

  • Efficacy and tolerance of a 6-month treatment course of daily interferon-alpha 2a for chronic hepatitis C with cirrhosis. The Australian Hepatitis C Study Group.

    abstract::Response to interferon-alpha (IFN-alpha) treatment in hepatitis C is poorer when cirrhosis is present. In the third Australian multicentre hepatitis C trial, Aushep-3, we examined the efficacy and tolerability of an intensive 24-week course of interferon-alpha 2a in Child-Pugh grade A patients with chronic hepatitis C...

    journal_title:Journal of viral hepatitis

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1046/j.1365-2893.1997.00062.x

    authors: Farrell G,Cooksley WG,Dudley FJ,Watson K

    更新日期:1997-09-01 00:00:00

  • Vaccines and immunotherapies against hepatitis B and hepatitis C viruses.

    abstract::Both hepatitis B and hepatitis C viruses (HBV and HCV) cause chronic infections worldwide that are associated with development of liver diseases ranging from mild liver inflammation to hepatocellular carcinomas. While efficient preventive vaccines are available for HBV, efforts are ongoing to develop one in case of HC...

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章,评审

    doi:10.1111/j.1365-2893.2007.00922.x

    authors: Inchauspé G,Michel ML

    更新日期:2007-11-01 00:00:00

  • Long-term interferon-alpha treatment of children with chronic hepatitis delta: a multicentre study.

    abstract::We assessed the efficacy of prolonged interferon-alpha (IFN) therapy in children with chronic hepatitis caused by hepatitis delta virus (HDV) by treating 26 paediatric cases with IFN-alpha 2b (5 MU m-2, then 3 MU m-2 three times weekly for 12 (medium-term group MTG) or 24 months (long-term group, LTG). Compliance and ...

    journal_title:Journal of viral hepatitis

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1111/j.1365-2893.1996.tb00002.x

    authors: Di Marco V,Giacchino R,Timitilli A,Bortolotti F,Crivellaro C,Calzia R,Iannuzzi C,Prestileo T,Vajro P,Nebbia G,Stringhi C,Rosina F,Biassoni D,Callea F,Rizzetto M,Craxi A

    更新日期:1996-05-01 00:00:00

  • Flaviviridae polymerase and RNA replication.

    abstract::Sequence motifs within the non-structural protein NS5 or NS5B of the members of the family Flaviviridae suggest that this protein is the RNA-dependent RNA polymerase. This protein has now been expressed in various in vitro systems and used in polymerase assays. To understand the role of the RNA polymerase in RNA repli...

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章,评审

    doi:10.1046/j.1365-2893.1999.00173.x

    authors: Bartholomeusz A,Thompson P

    更新日期:1999-07-01 00:00:00

  • High prevalence of hantavirus infection in a group of Chinese patients with acute hepatitis of unknown aetiology.

    abstract::In southwestern China, small but substantial numbers of patients with acute hepatitis were found without known hepatropic viral infections (hepatitis A, B, C, D or E, cytomegalovirus, Epstein-Barr virus) and were receiving no hepatotoxic drugs. Prevalence of antibodies, both neutralizing and specific immunoglobulin (I...

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章

    doi:10.1046/j.1365-2893.1997.00140.x

    authors: Meng G,Lan Y,Nakagawa M,Maehara T,Mitani K,Tomiyama T,Che XG,Ohkubo A

    更新日期:1997-07-01 00:00:00

  • Hepatitis C virus NS4 protein impairs the Th1 polarization of immature dendritic cells.

    abstract::Dendritic cells (DCs) in chronic hepatitis C patients display impaired function, although the details remain unclear. To investigate the hepatitis C virus (HCV) protein that has the most impact on DC function, we compared five recombinant proteins and seven HCV protein genes in modulating DC phenotype and function. Im...

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章

    doi:10.1111/j.1365-2893.2009.01213.x

    authors: Takaki A,Tatsukawa M,Iwasaki Y,Koike K,Noguchi Y,Shiraha H,Sakaguchi K,Nakayama E,Yamamoto K

    更新日期:2010-08-01 00:00:00

  • Low recurrence rate of hepatocellular carcinoma following ledipasvir and sofosbuvir treatment in a real-world chronic hepatitis C patients cohort.

    abstract::The aims of the present study were to evaluate the efficacy and tolerability of ledipasvir/sofosbuvir (LDV/SOF) with or without ribavirin in the treatment of chronic hepatitis C (CHC) in patients with advanced liver disease and to analyse whether the use of LDV/SOF treatment is associated with a new occurrence of hepa...

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章

    doi:10.1111/jvh.13075

    authors: Idilman R,Demir M,Aladag M,Erol C,Cavus B,Iliaz R,Koklu H,Cakaloglu Y,Sahin M,Ersoz G,Koksal İ,Karasu Z,Ozgenel M,Turan İ,Gunduz F,Ataseven H,Akdogan M,Kiyici M,Koksal AS,Akhan S,Gunsar F,Tabak F,Kaymakoglu S

    更新日期:2019-06-01 00:00:00

  • Serum PAI-1 is a novel predictor for response to pegylated interferon-α-2b plus ribavirin therapy in chronic hepatitis C virus infection.

    abstract::Obesity and insulin resistance have been reported as negative predictors for sustained virological response (SVR) in hepatitis C virus (HCV) genotype 1 infected patients treated with pegylated interferon-α plus ribavirin. They are also known to affect serum levels of several cytokines including adipocytokines. But the...

    journal_title:Journal of viral hepatitis

    pub_type: 杂志文章

    doi:10.1111/j.1365-2893.2011.01516.x

    authors: Miki D,Ohishi W,Ochi H,Hayes CN,Abe H,Tsuge M,Imamura M,Kamatani N,Nakamura Y,Chayama K

    更新日期:2012-02-01 00:00:00