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

ABSTRACT: 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?×?10(7)?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.

SUBMITTER: Wang YC

PROVIDER: S-EPMC4941731 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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

Wang Yin-Chen YC Yang Sien-Sing SS Su Chien-Wei CW Wang Yuan-Jen YJ Lee Kuei-Chuan KC Huo Teh-Ia TI Lin Han-Chieh HC Huang Yi-Hsiang YH

Scientific reports 20160712

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 ...[more]

PMID: 27405043

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Project description:Background and aim: Conventional hepatitis C treatment using pegylated interferon (PEG-IFN) and ribavirin is associated with significant side effects. IL28B polymorphism can predict response to treatment, with CC genotype having a better response. ITPA gene deficiency protects against clinically significant anaemia induced by treatment. The purpose of this study was to determine IL28B polymorphism and ITPA variation among hepatitis C genotype 1 patients who have undergone therapy with PEG-IFN and ribavirin and their association with sustained viral response (SVR). Methods: All hepatitis C genotype 1 patients who had been treated with PEG-IFN and ribavirin over the past 10 years were identified by available medical records and were contacted by letter of invitation to participate in the study. Blood samples for IL28B and ITPA genotyping were obtained. Medical records were reviewed for verification of treatment response, development of anaemia and if treatment reduction was required during the treatment. Results: A total of 61 patients with hepatitis C genotype 1 were treated with PEG-IFN and ribavirin, of whom 42 agreed to participate in the study. Mean age was 45.6±12.9 years at time of treatment, and 83.3% of patients were males. Thirty-three (78.6%) had IL28B CC genotype, of whom 25 (75.8%) obtained SVR compared with only 3 of 9 (33.3%) non C/C genotype patients who achieved SVR (P=0.041). Eleven (26.1%) patients had ITPA AC genotype, and 30 (71.4%) had CC genotype. There was no statistically significant difference between ITPA AC and CC genotypes in predicting clinically significant anaemia (45.5% vs 63.3%, P=0.302). Even among patients who developed anaemia, 70.8% still managed to achieve SVR. Treatment reduction also had no impact on SVR. Conclusion: Hepatitis C genotype 1 patients should be informed of the response rate for treatment with PEG-IFN and ribavirin in a population with favourable IL28B genotype before consideration of newer therapeutic options.

Project description:BackgroundPatients with chronic hepatitis C (HCV) infection have high prevalence of vitamin D deficiency. Genome-wide association study data has showed that several genetic variants within vitamin D cascade affect vitamin D function. This study aimed to determine whether genetic polymorphisms of genes in the vitamin D pathway are associated with treatment responses to pegylated interferon (PEG-IFN)-based therapy in patients with chronic HCV infection.MethodsThe study included 623 Thai patients from 2 university hospitals diagnosed with chronic HCV infection who were treated with a PEG-IFN and ribavirin. Patients were genotyped for functional variants on vitamin D synthetic pathway including GC (rs4588, rs7041, rs22020, rs2282679), CYP2R1 (rs2060793, rs12794714), CYP27B1 (rs10877012), and DHCR7 (rs12785878). Pre-treatment predictors of sustained virologic response (SVR) at 24 weeks following discontinuation of therapy were identified using a logistic regression analysis.ResultsSVR was achieved by 60.5% of patients (52.9% with HCV genotype 1; 66.7% with HCV non-genotype 1). In 44.6% of HCV genotype 1-infected patients, only the variant rs12785878 in the DHCR7 locus was significantly associated with an SVR. HCV genotype 1 patients who had DHCR7 rs12785878 GT/TT had a higher rate of SVR than those with the GG allele (59.7% vs. 43.4%, P = 0.03), but in HCV non-genotype 1-infected patients, the SVR rate did not differ between the two groups (63.3% and 59.1% for GT/TT and GG allele, P = 0.54). By multivariate analysis, liver fibrosis stage 0-1 (OR = 5.00; 95% CI, 2.02-12.37; P < 0.001), and DHCR7 rs12785878 GT/TT allele (OR = 2.69; 95% CI, 1.03-7.05; P = 0.04) were independent pre-treatment predictors of SVR following PEG-IFN-based therapy in HCV genotype 1 patients. Baseline HCV RNA < 400,000 IU/ml (OR = 1.96; 95% CI, 1.13-3.39; P = 0.02) was the only independent predictor of SVR in HCV non-genotype 1 patients. The polymorphisms of GC, CYP2R1 and CYP27B1 were not associated with treatment outcome even in genotype 1 or non-genotype 1 HCV infection.ConclusionThe DHCR7 polymorphism may be a pre-treatment predictive marker for response to PEG-IFN-based therapy in chronic HCV genotype 1 infection.

Project description:AIM:To evaluate the efficacy of pegylated interferon in Iranian chronic hepatitis C patients in relation to interferon-? (IFNL) polymorphisms. METHODS:This study enrolled patients with chronic hepatitis C referred to the Tehran Blood Transfusion Hepatitis Clinic in 2011. Patients were included in the study if they had no concomitant hepatic illness, were negative for human immunodeficiency virus antibodies, and had no prior history of treatment with any type of pegylated interferon. Patients were treated with 180 ?g pegylated interferon alpha-2a (Pegaferon(®)) weekly and 800-1200 mg ribavirin daily for 24 or 48 wk depending on weight and hepatitis C virus (HCV) genotype. Blood samples were collected from patients to obtain DNA for determination of IFNL rs12979860 and rs8099917 polymorphisms. The virologic response in patients was then evaluated and compared between the different IFNL genotypes. RESULTS:A total of 152 patients with a mean age of 41.9 ± 10.0 years were included in the study, of which 141/152 were men (92.8%). The most frequent HCV genotype was type-1, infecting 93/152 (61.2%) patients. Sustained virologic response (SVR) was achieved in 81.9% of patients with HCV genotype-1 and 91.1% of patients with HCV genotype-3. Treatment success was achieved in 91.2% (52/57) of patients with the IFNL rs12979860 CC genotype and 82.1% (78/95) in those with other genotypes. Similar treatment response rates were also observed in patients with rs8099917 TT (39/45; 86.7%) and non-TT (61/68; 89.7%) genotypes. Univariate analyses identified the following factors which influenced treatment response for inclusion in a multivariate analysis: age, HCV RNA level, stage of liver fibrosis, rs12979860 CC genotype, and aspartate transaminase level. A logistic regression analysis revealed that only the rs12979860 CC genotype was significantly associated with achievement of SVR (OR = 6.2; 95%CI: 1.2-31.9; P = 0.03). CONCLUSION:The rs12979860 CC genotype was associated with SVR in patients receiving pegylated interferon plus ribavirin, however, the SVR rate in other rs12979860 genotypes was also relatively high.

Project description:Vitamin D receptor (VDR) modulates host immune responses to infections such as hepatitis C virus (HCV) infection, including interferon signaling. This study aimed to investigate the associations of VDR polymorphisms with advanced liver fibrosis and response to pegylated interferon (PEG-IFN)-based therapy in patients with chronic HCV infection. In total, 554 Thai patients with chronic HCV infection treated with a PEG-IFN-based regimen were enrolled. Six single-nucleotide polymorphisms (SNPs) were genotyped: the IL28B C > T (rs12979860) SNP and five VDR SNPs, comprising FokI T > C (rs2228570), BsmI C > T (rs1544410), Tru9I G > A (rs757343), ApaI C > A (rs7975232), and TaqI A > G (rs731236). In total, 334 patients (60.3%) achieved sustained virological response (SVR), and 255 patients (46%) were infected with HCV genotype 1. The bAt (CCA) haplotype, consisting of the BsmI rs1544410 C, ApaI rs7975232 C, and TaqI rs731236 A alleles, was associated with poor response (in terms of lack of an SVR) to PEG-IFN-based therapy. The IL28B rs12979860 CT/TT genotypes (OR = 3.44, 95% CI [2.12-5.58], p < 0.001), bAt haplotype (OR = 2.02, 95% CI [1.04-3.91], p = 0.03), pre-treatment serum HCV RNA (logIU/mL; OR = 1.73, 95% CI [1.31-2.28], p < 0.001), advanced liver fibrosis (OR = 1.68, 95% CI [1.10-2.58], p = 0.02), and HCV genotype 1 (OR = 1.59, 95% CI [1.07-2.37], p = 0.02) independently predicted poor response. Patients with the bAt haplotype were more likely to have poor response compared to patients with other haplotypes (41.4% vs 21.9%, p = 0.03). The FokI rs2228570 TT/TC genotypes (OR = 1.63, 95% CI [1.06-2.51], p = 0.03) and age ?55 years (OR = 2.25; 95% CI [1.54-3.32], p < 0.001) were independently associated with advanced liver fibrosis, assessed based on FIB-4 score >3.25. VDR polymorphisms were not associated with pre-treatment serum HCV RNA. In Thai patients with chronic HCV infection, the bAt haplotype is associated with poor response to PEG-IFN-based therapy, and the FokI rs2228570 TT/TC genotypes are risk factors for advanced liver fibrosis.

Project description:Patients receiving therapy for chronic hepatitis C virus (HCV) infection frequently experience cytopenias and weight loss. We retrospectively assessed the pharmacodynamic effects of pegylated interferon (PEG-IFN) alfa-2a and ribavirin by evaluating the relationship between changes in hematologic parameters, body weight, and virologic response. Patients with HCV genotypes 1, 4, 5, or 6 receiving 24 or 48 weeks of PEG-IFN alfa-2a and ribavirin therapy were pooled from four phase 3/4 trials. Maximum decreases in hemoglobin level, neutrophil count, platelet count, and weight during therapy were assessed according to virologic response category (sustained virologic response [SVR], relapse, breakthrough, and nonresponder) and race/ethnicity. Of 1,778 patients analyzed, more than half were male, non-Hispanic Caucasian, and infected with HCV genotype 1; had a baseline HCV RNA >800,000; and had alanine aminotransferase levels ?3 × the upper limit of normal. Virologic responders (SVR, relapse, and breakthrough) experienced greater maximum decreases from baseline in hemoglobin level, neutrophil count, platelet count, and weight compared with nonresponders; however, no clear trend was observed between SVR, relapse, and breakthrough. After adjusting for drug exposure and treatment duration, only decreases in neutrophil count remained associated with virologic response. Significantly greater declines in neutrophil (P < 0.0001) and platelet (P < 0.005) count were observed at weeks 4, 12, and 24 of therapy in virologic responders compared with nonresponders. This difference between responders and nonresponders was also observed among racial/ethnic groups, although statistical significance was not consistent across all groups.This post hoc analysis of HCV patients treated with PEG-IFN alfa-2a and ribavirin shows that maximum decreases from baseline in hematologic parameters and weight loss were associated with virologic response. However, after adjusting for drug exposure and accounting for duration of therapy, only neutropenia was independently associated with virologic response.

Dataset Information

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

Publications

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

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