CXCL9 Associated with Sustained Virological Response in Chronic Hepatitis B Patients Receiving Peginterferon Alfa-2a Therapy: A Pilot Study

Lee, I‐Cheng; Huang, Yi Hsiang; Su, Chien–Wei; Wang, Yuan‐Jen; Huo, Teh–Ia; Lee, Kuei–Chuan; H, Lin

doi:10.1371/journal.pone.0076798

Cited by 21 publications

(12 citation statements)

References 43 publications

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“…Previous studies were not able to identify definite pretreatment factors that can predict the treatment response to PEG-IFN in HBeAg-negative cases. Our previous study suggested that a baseline CXCL9 level is associated with the response to PEG-IFN 16 . A further study to combine baseline HBsAg of <1250 IU/mL and a high CXCL9 level might improve the prediction rate for HBeAg-negative CHB in the future.…”

Section: Discussionmentioning

confidence: 96%

“…Several prediction factors are known to be associated with treatment response among PEG-IFN treated patients based on previous clinical trials. In HBeAg-positive CHB patients, a high alanine aminotransferase (ALT) level, a low HBV viral load at baseline, genotype A HBV, and a decline in serum HBsAg level during the treatment have been associated with a clinical response in previous studies 14 15 16 17 . Among HBeAg-negative CHB patients, very few baseline predictors have been proposed and a response-guided treatment according to serial HBsAg decline is recommended 18 19 20 21 22 23 .…”

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confidence: 99%

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Predictors of response to pegylated interferon in chronic hepatitis B: a real-world hospital-based analysis

Wang

Yang

et al. 2016

Sci Rep

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Information on the efficacy of pegylated interferon (PEG-IFN) treatment of chronic hepatitis B (CHB) patients and predictors of the response based on real-world data is limited. Consecutive 201 patients who underwent PEG-IFN treatment for CHB were reviewed. A virological response (VR) was defined as a serum HBV DNA of <2000 IU/mL, and a combined response (CR) was defined a VR accompanied by serological response for hepatitis B e antigen (HBeAg)-positive CHB. For HBeAg-positive CHB patients, the HBeAg seroconversion rate and CR rate were 30.5% and 21.2% at 48 weeks after end of treatment (EOT), respectively. Baseline alanine aminotransferase (ALT) level was associated with HBeAg seroconversion, while baseline hepatitis B s antigen (HBsAg) levels of <250 IU/mL and HBV DNA <2.5 × 107 IU/mL were strongly associated with sustained off-treatment CR. For HBeAg-negative CHB, the VR rates were 85.5%, and 27.7% at EOT, and 48 weeks after EOT, respectively; a baseline HBsAg <1,250 IU/mL was associated with sustained off-treatment VR. PEG-IFN treatment has durable HBeAg seroconversion in HBeAg-positive CHB, but results in a high risk of relapse among HBeAg-negative CHB patients. Pre-treatment HBsAg level is an important predictor of VR in CHB patients undergoing PEG-IFN treatment.

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Section: Discussionmentioning

confidence: 96%

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confidence: 99%

Predictors of response to pegylated interferon in chronic hepatitis B: a real-world hospital-based analysis

Wang

Yang

et al. 2016

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“…Therefore, it is also very important to understand the immunopathogenesis of hepatocyte inflammation. The natural course of CHB and treatment response of the individual patient will be determined partly by the unique strain of the HBV and mainly by the genetic characteristics of the individual, including polymorphisms and the expressed gene profile 5 6 7 8 9 .…”

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confidence: 99%

Liver Gene Expression Profiles Correlate with Virus Infection and Response to Interferon Therapy in Chronic Hepatitis B Patients

Hsiao

Chen

et al. 2016

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The natural course of chronic hepatitis B (CHB) infection and treatment response are determined mainly by the genomic characteristics of the individual. We investigated liver gene expression profiles to reveal the molecular basis associated with chronic hepatitis B and IFN-alpha (IFNα) treatment response in CHB patients. Expression profiles were compared between seven paired liver biopsy samples taken before and 6 months after successful IFNα treatment or between pretreatment biopsy samples of 11 IFNα responders and 11 non-responders. A total of 132 differentially up-regulated and 39 down-regulated genes were identified in the pretreated livers of CHB patients. The up-regulated genes were mainly related to cell proliferation and immune response, with IFNγ and B cell signatures significantly enriched. Lower intrahepatic HBV pregenomic RNA levels and 25 predictive genes were identified in IFNα responders. The predictive gene set in responders significantly overlapped with the up-regulated genes associated with the pretreated livers of CHB patients. The mechanisms responsible for IFNα treatment responses are different between HBV and HCV patients. HBV infection evokes significant immune responses even in chronic infection. The up-regulated genes are predictive of responsiveness to IFNα therapy, as are lower intrahepatic levels of HBV pregenomic RNA and pre-activated host immune responses.

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“…The lack of a difference in the MIG levels depending on the treatment response in earlier studies may be explained by the much smaller number of patients included in those studies and/or the difference in patient ethnicity in this study compared to previous studies . Interestingly, it has been described that HBV‐infected patients treated with pegIFNα‐2a who achieved SVR had higher MIG plasma levels at baseline than non‐SVR patients . Thus, higher MIG plasma levels at baseline may be an indicator of a favourable response to pegIFN treatment both in HCV‐ and HBV‐infected patients.…”

Section: Discussionmentioning

confidence: 73%

“…This could explain why higher MIG levels and the correlation between IP-10 and MIG levels associate with a successful response to treatment. Reports from studies in HBV-infected patients describing a positive correlation between IP-10 and MIG (28) and an association of higher IP-10 levels with response to IFN treatment (33,34) together suggest a balanced ratio between IP-10 and MIG in these patients.…”

Section: Discussionmentioning

confidence: 91%

High MIG (CXCL9) plasma levels favours response to peginterferon and ribavirin in HCV‐infected patients regardless of DPP4 activity

Johansson

Talloen

Tuefferd

et al. 2015

Liver International

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Background & Aims Sustained virological response (SVR) following peginterferon (pegIFN) and ribavirin (RBV) treatment in hepatitis C virus (HCV) infected patients has been linked with the IL28B genotype and lower peripheral levels of the CXCR3-binding chemokine IP-10 (CXCL10). To further improve the understanding of these biomarkers we investigated plasma levels of the other CXCR3-binding chemokines and activity of the dipeptidyl peptidase IV (DPP4, CD26) protease, which cleaves IP-10, in relation to treatment response. Methods African-American and Caucasian HCV genotype 1 infected patients (n=401) were treated with pegIFN/RBV for 48 weeks (ViraHep-C cohort). Pretreatment plasma levels of MIG (CXCL9), I-TAC (CXCL11) and the type III interferon IL29 were investigated by Luminex and DPP4 activity by using a luciferase assay. Results Patients achieving SVR had higher baseline MIG plasma levels and lower DPP4 activity than non-SVR patients. MIG was higher in Caucasians, IL28B CC (rs1297860) genotype carriers and patients with higher ALT levels. MIG correlated with IP-10 in SVR patients, but not in non-SVRs. A high DPP4 activity correlated with higher IP-10 levels, while DPP4 activity was not associated with MIG or I-TAC levels. Conclusions The associations of MIG with SVR status and IL28B genotype imply that higher MIG plasma levels could reflect a beneficial immunological state for response to pegIFN/RBV treatment. The correlation between MIG and IP-10 observed only in SVR patients may contribute to a better treatment response whereas this MIG/IP-10 balance might be disrupted in non-SVR patients due to increased DPP4 cleavage of IP-10 into a dysfunctional form.

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CXCL9 Associated with Sustained Virological Response in Chronic Hepatitis B Patients Receiving Peginterferon Alfa-2a Therapy: A Pilot Study

Cited by 21 publications

References 43 publications

Predictors of response to pegylated interferon in chronic hepatitis B: a real-world hospital-based analysis

Predictors of response to pegylated interferon in chronic hepatitis B: a real-world hospital-based analysis

Liver Gene Expression Profiles Correlate with Virus Infection and Response to Interferon Therapy in Chronic Hepatitis B Patients

High MIG (CXCL9) plasma levels favours response to peginterferon and ribavirin in HCV‐infected patients regardless of DPP4 activity

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