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  • SAGE Publications  (11)
  • Chen, Pei-Jer  (11)
  • 1
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    Influence of Metabolic Syndrome, Viral Genotype and Antiviral Therapy on Superimposed Fatty Liver Disease in Chronic Hepatitis C
    SAGE Publications ; 2005
    In:  Antiviral Therapy Vol. 10, No. 3 ( 2005-04), p. 405-415
    Details
    In: Antiviral Therapy, SAGE Publications, Vol. 10, No. 3 ( 2005-04), p. 405-415
    Abstract: The prevalence and clinical implications of non-alcoholic fatty liver disease in patients with chronic hepatitis C remain unknown in Taiwan. Methods We addressed the relevant issues by analysing 95 naive Taiwanese patients infected with either hepatitis C virus (HCV) genotype 1 ( n=57) or 2 ( n=38), receiving interferon alone ( n=41) or in combination with ribavirin ( n=54) therapy. A single pathologist scored steatosis and steatohepatitis at baseline and 24 weeks after antiviral treatment. Results At baseline, steatosis and steatohepatitis were present in 44 (46%) and four (4%) patients, respectively. Variables associated with steatosis in logistical regression were hyperglycaemia ( P=0.01), hypertriglyceridaemia ( P=004) and body mass index ≥27 ( P=0.009), but not HCV genotype or viral load. The grade of steatosis correlated well with the number of metabolic syndrome parameters ( P=0.018). Interferon monotherapy, advanced age and HCV genotype 1, but not steatosis, correlated with lower sustained response rate. After treatment, steatosis improved in 19 and worsened in nine, which also did not correlate with HCV genotype ( P=0.850) or sustained response to antiviral therapy ( P=0.246). Conclusions Hepatic steatosis in Taiwanese patients with chronic hepatitis C was associated with features of the metabolic syndrome, but did not correlate with HCV genotype, advanced fibrosis or the response to antiviral therapy.
    Type of Medium: Online Resource
    ISSN: 1359-6535 , 2040-2058
    URL: Article
    DOI: 10.1177/135965350501000302
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2005
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  • 2
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    Interleukin 28B Genetic Polymorphisms and Viral Factors Help Identify HCV Genotype-1 Patients who Benefit from 24-Week Pegylated Interferon plus Ribavirin Therapy
    SAGE Publications ; 2012
    In:  Antiviral Therapy Vol. 17, No. 3 ( 2012-04), p. 477-484
    Details
    In: Antiviral Therapy, SAGE Publications, Vol. 17, No. 3 ( 2012-04), p. 477-484
    Abstract: Interleukin 28B (IL28B) single nucleotide polymorphism (SNP) genotypes and viral factors can predict sustained virological response (SVR) in HCV genotype-1 (HCV-1) patients receiving 48 weeks of pegylated interferon and ribavirin. Whether these factors would identify those patients who can benefit from a shorter duration of therapy remains unclear. Methods Treatment-naive HCV-1 patients ( n=662) receiving 24 or 48 weeks of combination therapy were enrolled. Baseline demographic data, HCV viral load, IL28B SNP genotypes (rs8099917), duration of therapy and rapid virological response (RVR) were evaluated to predict SVR. The SVR rates were further stratified by the independent factors and compared. Results The IL28B rs8099917 TT genotype, low baseline viral load (HCV RNA≤600,000 IU/ml), RVR and 48-week therapy independently predicted SVR. In RVR patients with the IL28B rs8099917 TT genotype, the SVR rate of 24-week therapy was comparable to 48-week therapy (95% versus 99%; P=0.21) at low baseline viral load, but was inferior to 48-week therapy (70% versus 97%; P 〈 0.001) at high baseline viral load. In non-RVR patients, the SVR rate of 24-week therapy was inferior to 48-week therapy for those with the IL28B rs8099917 TT genotype but high baseline viral load (23% versus 62%; P 〈 0.001), and those with the IL28B rs8099917 GT/GG genotype but low baseline viral load (0% versus 33%; P=0.02). Conclusions HCV-1 patients simultaneously bearing the IL28B rs8099917 TT genotype, low baseline viral load and RVR can benefit from a shorter duration of combination therapy.
    Type of Medium: Online Resource
    ISSN: 1359-6535 , 2040-2058
    URL: Article
    DOI: 10.3851/IMP2026
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2012
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  • 3
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    Reduced Toll-Like Receptor 3 Expression in Chronic Hepatitis B Patients and Its Restoration by Interferon Therapy
    SAGE Publications ; 2013
    In:  Antiviral Therapy Vol. 18, No. 7 ( 2013-10), p. 877-884
    Details
    In: Antiviral Therapy, SAGE Publications, Vol. 18, No. 7 ( 2013-10), p. 877-884
    Abstract: Toll-like receptor (TLR)3 gene variants may correlate with clinical significance of chronic viral infections including HBV. We aimed to investigate the expression of TLR3 in peripheral blood mononuclear cells (PBMCs) and liver cells of chronic hepatitis B (CHB) patients and its response to pegylated interferon or nucleoside analogue therapy. Methods We consecutively enrolled 127 CHB patients and 64 hepatitis B surface antigen-negative, anti-HCV-negative healthy individuals as controls. We compared the TLR3 expressions on fresh PBMCs and liver cells from patients and controls, before and during pegylated interferon or nucleoside analogue therapy. Results Compared to controls, patients had a lower TLR3 mean fluorescence intensity (MFI) on PBMCs (mean ±sd 14.61 ±13.49 versus 9.70 ±4.61; P 〈 0.001), independent of age, gender and alanine aminotransferase (ALT; -13.466, 95% CI -17.202, -9.730; P 〈 0.001). Patients had limited TLR3 stains on Kupffer cells, whereas controls had diffuse stains on Kupffer and hepatocytes. Hepatic TLR3 messenger RNA was lower in patients than controls (0.47 ±0.30 versus 1-fold). Using pretreatment TLR3 MFI as a referent, among 5 of 12 pegylated-interferon-treated patients with sustained virological response (SVR), TLR3 MFI was restored to a mean of 1.5- to 1.7-folds immediately after treatment. Among seven non-responders or relapsers, TLR3 MFI reduced to a mean of 0.5- to 0.7-fold. Among 10 entecavir-treated patients with on-treatment virological response, TLR3 MFI gradually was restored to a mean of 1.2-folds during 48-week therapy. Conclusions CHB patients have reduced TLR3 expression on PBMCs, independent of age, gender and ALT, and on liver cells. Patients with pegylated-interferon-induced SVR have a more significant restoration of TLR3 expression than those under entecavir.
    Type of Medium: Online Resource
    ISSN: 1359-6535 , 2040-2058
    URL: Article
    DOI: 10.3851/IMP2630
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2013
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  • 4
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    Serum hepatitis B surface antigen concentration correlates with HBV DNA level in patients with chronic hepatitis B
    SAGE Publications ; 2010
    In:  Antiviral Therapy Vol. 15, No. 8 ( 2010-11), p. 1133-1139
    Details
    In: Antiviral Therapy, SAGE Publications, Vol. 15, No. 8 ( 2010-11), p. 1133-1139
    Abstract: Serum HBV DNA level is crucial in the management of chronic hepatitis B (CHB); however, the assay is expensive and cannot be used widely. Therefore, we explored the possibility of hepatitis B surface antigen (HBsAg) quantification as a surrogate marker for HBV DNA level in CHB patients. Methods A total of 289 CHB patients were enrolled, 251 were evaluated at baseline and 75 of them were also evaluated during anti-HBV treatment. Another 38 on-treatment patients were used for validation. Serum HBsAg titre was quantified by an immunoassay and HBV DNA level by a PCR-based method. Baseline and on-treatment data were analysed. Results In parallel to log 10 HBV DNA, the log 10 HBsAg was high in both immune tolerance and immune clearance phases, and significantly decreased in the inactive carrier state and was again increased in the reactivation phase of the CHB infection. There was a positive correlation between log 10 HBsAg and log 10 HBV DNA, which was greater in patients with chronic hepatitis, hepatitis B e antigen- positivity, greater alanine aminotransferase or HBsAg levels at baseline and during pegylated interferon treatment. Log 10 HBsAg could predict log 10 HBV DNA independently. An HBsAg titre of 〉 900 IU/ml at baseline or 〉 1,500 IU/ml within the first year of treatment could predict an HBV DNA level of 〉 20,000 IU/ml, especially in subgroups of chronic hepatitis with alanine aminotransferase levels 〉 40 IU/l. The dynamics of HBsAg might also predict serial HBV DNA changes. In the validation group, 64% of patients with on-treatment HBV DNA levels 〉 20,000 IU/ml could be correctly predicted. Conclusions Serum HBsAg concentration might serve as a surrogate marker of HBV DNA level in CHB patients.
    Type of Medium: Online Resource
    ISSN: 1359-6535 , 2040-2058
    URL: Article
    DOI: 10.3851/IMP1696
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2010
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  • 5
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    Interleukin 28B Genetic Polymorphisms Play a Minor Role in Identifying Optimal Treatment Duration in HCV Genotype 1 Slow Responders to Pegylated Interferon plus Ribavirin
    SAGE Publications ; 2012
    In:  Antiviral Therapy Vol. 17, No. 6 ( 2012-08), p. 1059-1067
    Details
    In: Antiviral Therapy, SAGE Publications, Vol. 17, No. 6 ( 2012-08), p. 1059-1067
    Abstract: Pegylated interferon and ribavirin for 72 weeks improve sustained virological response (SVR) in HCV genotype 1 (HCV-1) slow viral responders. Whether interleukin 28B (IL28B) single nucleotide polymorphism (SNP) genotypes and on-treatment viral responses can identify non-rapid virological response (RVR) patients who benefit from 48 or 72 weeks of therapy remains unclear. Methods Treatment-naive HCV-1 patients who failed to achieve RVR were randomly assigned to receive 48 ( n=168) or 72 ( n=167) weeks of therapy. Baseline factors and on-treatment virological responses at weeks 8 and 12 were evaluated for SVR in 289 compliant patients who received ≥80% of drug dosages and treatment duration, and had end of follow-up viral response. The stratified SVR rates for independent factors were compared by treatment duration. Results Treatment duration, IL28B rs8099917 genotypes, cirrhosis, week-8 viral response (undetectable HCV RNA at treatment week 8) and complete early virological response (cEVR) predicted SVR. In week-8 viral response patients, the SVR rates of 72-week and 48-week treatment were similar (75–88%), regardless of IL28B SNP genotypes or cirrhosis. In non-week-8 viral response patients who achieved cEVR, the SVR rate of 72-week treatment was higher than that of 48-week treatment for non-cirrhotic patients, regardless of IL28B SNP genotypes (91–100% versus 13–44%; P=0.001). Conclusions Although IL28B SNP genotypes predict SVR, they play a minor role when on-treatment viral responses are taken into consideration. On-treatment viral responses at weeks 8 and 12 are the key determinants to decide the optimal treatment duration in HCV-1 patients without RVR.
    Type of Medium: Online Resource
    ISSN: 1359-6535 , 2040-2058
    URL: Article
    DOI: 10.3851/IMP2322
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2012
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  • 6
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    Hepatitis B virus genotype B has an earlier emergence of lamivudine resistance than genotype C
    SAGE Publications ; 2009
    In:  Antiviral Therapy Vol. 14, No. 8 ( 2009-11), p. 1157-1163
    Details
    In: Antiviral Therapy, SAGE Publications, Vol. 14, No. 8 ( 2009-11), p. 1157-1163
    Abstract: Hepatitis B virus (HBV) genotype B and C seem not to affect the therapeutic response to lamivudine (3TC). Whether a given genotype has an earlier emergence of 3TC resistance remains unclear. We thus conducted this study to elucidate the association of HBV genotype with the emergence of 3TC-resistant strains in Taiwanese patients. Methods Forty chronic hepatitis B patients who developed resistance after 3TC therapy were retrospectively enrolled. HBV genotype, serum alanine aminotransferase (ALT) and HBV DNA levels were determined at baseline. The presence of 3TC-resistant mutations was confirmed by direct sequencing whenever biochemical breakthrough developed. Results The distribution of HBV genotype B and C in 40 patients receiving 3TC therapy were 60% and 40%, respectively. The mean interval to detect 3TC- resistant strain was 19.6 ±1.7 months. By using multivariate analysis, HBV genotype B and higher pre-treatment HBV DNA level were independently associated with earlier detection of 3TC-resistant strains. In addition, genotype B was significantly associated with development of 3TC resistance within the first 12 months of 3TC therapy compared with genotype C (odds ratio 8.27; P=0.004). Conclusions Compared with HBV genotype C, genotype B appears to have an earlier biochemical resistance to 3TC than genotype C. Therefore, more frequent monitoring of viral load or genotypical resistance might be needed for patients with HBV genotype B infection receiving 3TC therapy, especially during the first year.
    Type of Medium: Online Resource
    ISSN: 1359-6535 , 2040-2058
    URL: Article
    DOI: 10.3851/IMP1454
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2009
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  • 7
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    Lack of Interferon Sensitivity-Determining Region in the Genome of Hepatitis B Virus Genotype Ba
    SAGE Publications ; 2004
    In:  Antiviral Therapy Vol. 9, No. 6 ( 2004-08), p. 895-903
    Details
    In: Antiviral Therapy, SAGE Publications, Vol. 9, No. 6 ( 2004-08), p. 895-903
    Abstract: In chronic hepatitis B, both host and viral factors may predict the response to interferon (IFN) treatment. Whether IFN sensitivity-determining regions exist within the hepatitis B virus (HBV) genomic background remains largely unknown. We therefore performed full-length viral genomic comparison between HBVs obtained from IFN responders and non-responders. Methods We enrolled 18 HBV genotype Ba patients who had received 24-week IFN 5 MU three times weekly and were followed monthly for 12 months post-treatment. There were 10 responders and eight non-responders. Pretreatment full-length viral nucleotide consensus sequence was obtained. In six non-responders and four responders, post-treatment viral nucleotide sequence was further compared with their corresponding pre-treatment specimens. In addition, the average number of nucleotide substitutions of the HBV quasispecies was compared between three responders and three non-responders. Results HBV nucleotide consensus sequence was identical between responders and non-responders. We found 0–15 (mean 7.7) nucleotide substitutions in the post-treatment HBV genome in the six non-responders and 0–14 (mean 3.8) nucleotide substitutions in the four responders, respectively. Genetic complexity of HBV quasispecies was comparable between responders and non-responders. Conclusions Our results suggest that an IFN sensitivity-determining region might not exist within the genome of HBV genotype Ba. Host factors and virus–host interactions may be more important in determining the response to IFN treatment.
    Type of Medium: Online Resource
    ISSN: 1359-6535 , 2040-2058
    URL: Article
    DOI: 10.1177/135965350400900603
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2004
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  • 8
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    Reduced Toll-Like Receptor 9 Expression on Peripheral C D14 + Monocytes of Chronic Hepatitis B Patients and its Restoration by Effective Therapy
    SAGE Publications ; 2014
    In:  Antiviral Therapy Vol. 19, No. 7 ( 2014-10), p. 637-643
    Details
    In: Antiviral Therapy, SAGE Publications, Vol. 19, No. 7 ( 2014-10), p. 637-643
    Abstract: Chronic hepatitis B (CHB) patients display Toll-like receptor 9 (TLR9)-dependent defective immune responses. We aimed to study TLR9 expression on CHB patients and its alteration during therapy. Methods We compared TLR9 expression on fresh peripheral CD14 + monocytes from a cohort of 97 CHB patients and 35 HBsAg-negative, anti-HCV-negative controls, during pegylated interferon or entecavir therapy. TLR9 expression on liver tissue was also investigated. Results Compared with controls, peripheral CD14 + monocytes of CHB patients displayed reduced expression of TLR9 mean fluorescence intensity (MFI; 9.90 ±3.64 versus 7.95 ±3.61; P=0.007) independent of age, gender and alanine aminotransferase (ALT; -2.09, 95% CI -3.568, -0.613; P=0.006). Furthermore, age, gender, ALT, HBeAg status, quantitative HBsAg (qHBsAg) or HBV DNA did not predict the TLR9 expression ( P=0.863). Hepatic TLR9 messenger RNA (mRNA) was significantly reduced in 54 patients compared with 3 controls (0.45 ±0.32 versus 1-fold). Using response-guided therapy by qHBsAg levels and pretreatment TLR9 MFI as a reference, TLR9 MFI restored to a mean of 1.7- to 2.7-fold in pegylated interferon responders and reduced to a mean of 0.6-to 0.7-fold in non-responders starting from treatment week 12. Among 10 entecavir-treated patients, TLR9 MFI gradually restored to a mean of 1.2- to 2.1-fold starting from treatment week 48. Conclusions CHB patients display reduced TLR9 expression on peripheral CD14 + monocytes, which is independent of host and viral markers, and on liver tissue. Responders to pegylated interferon and those under entecavir demonstrate restoration of TLR9 expression. On-treatment TLR9 expression on peripheral monocytes might predict response to pegylated interferon therapy.
    Type of Medium: Online Resource
    ISSN: 1359-6535 , 2040-2058
    URL: Article
    DOI: 10.3851/IMP2762
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2014
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  • 9
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    Effect of Host and Viral Factors on Hepatitis B E Antigen-Positive Chronic Hepatitis B Patients Receiving Pegylated Interferon-α-2A Therapy
    SAGE Publications ; 2011
    In:  Antiviral Therapy Vol. 16, No. 5 ( 2011-07), p. 629-637
    Details
    In: Antiviral Therapy, SAGE Publications, Vol. 16, No. 5 ( 2011-07), p. 629-637
    Abstract: Pegylated interferon (PEG-IFN)-α-2a improves the hepatitis B e antigen (HBeAg) seroconversion rate in HBeAg-positive chronic hepatitis B patients. However, baseline factors predicting favourable responses to PEG-IFN-α-2a remain largely unknown. Methods A total of 115 HBeAg-positive chronic hepatitis B patients who had a pre-therapy serum alanine amino-transferase (ALT) level over two times the upper limit of normal and received PEG-IFN-α-2a for 6–12 months were consecutively enrolled according to the local reimbursed guidelines. HBeAg seroconversion and combined response defined as HBeAg seroconversion, HBV-DNA level 〈 20,000 IU/ml as well as ALT normalization at 6 months off therapy were primary and secondary therapeutic end points, respectively. Baseline viral factors, including viral load, genotype and major sequences of precore stop codon/ basal core promoter (BCP), and host factors, including three single nucleotide polymorphisms among the HLA-DPA1, HLA-DPB1 and IL28B regions, were determined to correlate with therapeutic end points. Results HBeAg seroconversion and combined response rates were 26.1% and 18.3%, respectively. By multivariate analysis, BCP mutation (OR 8.04, 95% CI 2.00-32.28) and rs3077 G/G genotype (OR 3.49, 95% CI 1.12-10.84) were associated with a higher HBeAg seroconversion rate; BCP mutation (OR 9.28, 95% CI 1.92-44.99) and baseline viral load 〈 2x10 6 IU/ml (OR 4.78, 95% CI 1.37-16.69) were associated with a higher combined response rate. Conclusions BCP mutation is associated with higher HBeAg seroconversion and combined response rates at 6 months off therapy in HBeAg-positive chronic hepatitis B patients treated with PEG-IFN-α-2a. Genetic variants in the HLA-DPA1 region may also affect treatment-induced HBeAg seroconversion.
    Type of Medium: Online Resource
    ISSN: 1359-6535 , 2040-2058
    URL: Article
    DOI: 10.3851/IMP1841
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2011
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  • 10
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    Factors affecting early viral load decline of Asian chronic hepatitis C patients receiving pegylated interferon plus ribavirin therapy
    SAGE Publications ; 2009
    In:  Antiviral Therapy Vol. 14, No. 1 ( 2009-01), p. 45-54
    Details
    In: Antiviral Therapy, SAGE Publications, Vol. 14, No. 1 ( 2009-01), p. 45-54
    Abstract: Early viral load decline following pegylated interferon-α2a and ribavirin therapy is an important predictor of the treatment responses in chronic hepatitis C (CHC) patients, thus, it is essential to evaluate the influence of host and viral factors on early viral load decline. Methods Clinical and serial virological data were collected from 145 consecutive Asian CHC patients with pegylated interferon-α2a plus ribavirin therapy. A dose of pegylated interferon-α2a was administered at week 1 and then weekly with daily oral ribavirin for 24 or 48 weeks. Genotyping and quantification of hepatitis C virus (HCV) RNA were done using molecular methods. Results A total of 81 patients were infected with HCV genotype 1, 61 with genotype 2 and 3 with both genotypes 1 and 2. At the end of follow-up, 110 patients attained sustained virological response (SVR). In multivariate analyses, body mass index (BMI) and genotype were related to viral load decline at day 2, baseline viral load and high-density lipoprotein (HDL) cholesterol levels were correlated with viral load decline between days 2 and 28. Genotype, baseline viral load, alanine aminotransferase (ALT) levels and BMI independently predicted rapid virological response, whereas only genotype 2, lower baseline viral load and more substantial viral load decline at day 28 predicted a higher SVR. Conclusions HCV genotype, baseline viral load, pretreatment BMI, HDL and ALT levels have a significant effect on early viral load decline of Asian CHC patients with interferon-based therapy. Only HCV genotype, baseline viral load and viral load decline at day 28 can independently predict SVR.
    Type of Medium: Online Resource
    ISSN: 1359-6535 , 2040-2058
    URL: Article
    DOI: 10.1177/135965350901400101
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2009
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