scholarly journals Predictors of response to pegylated interferon treatment in HBeAg-negative patients with chronic hepatitis B

2014 ◽  
Vol 8 (12) ◽  
pp. 1601-1608 ◽  
Author(s):  
Ertugrul Guclu ◽  
Nazan Tuna ◽  
Oguz Karabay ◽  
Sıla Akhan ◽  
Hurrem Bodur ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Tertiary Care ◽  
Pegylated Interferon ◽  
Virologic Response ◽  
Hbv Dna ◽  
The Third ◽  
Predictors Of Response ◽  
Number Of Patients

Introduction: Although pegylated interferons (pegIFNs) alpha-2a and alpha-2b have been used in chronic hepatitis B (CHB) treatment for many years, there are few studies concerning predictors of sustained virologic response (SVR) to pegIFN therapy. In this study, we aimed to investigate the predictors of response to pegIFN treatment in cases with HBeAg-negative CHB infection. Methodology: Seventeen tertiary care hospitals in Turkey were included in this study. Data from consecutively treated HBeAg-negative CHB patients, who received either pegIFN alpha-2a or alpha-2b, were collected retrospectively. SVR is defined as an HBV DNA concentration of less than 2,000 IU/mL six months after the completion of therapy Results: SVR was achieved in 40 (25%) of the 160 HBeAg-negative CHB patients. Viral loads in patients with SVR were lower compared to those with no SVR, beginning in the third month of treatment (p < 0.05). The number of cases with a decline of 1 log10 IU/mL in viral load after the first month of treatment and with a serum HBV DNA level under 2,000 IU/mL after the third month of treatment was higher in cases with SVR (p < 0.05). The number of patients who had undetectable HBV DNA levels at week 48 among responders was significantly greater than among post-treatment virological relapsers (p < 0.05). Conclusions: Detection of a 1 log10 decline in serum HBV DNA level at the first month of treatment and a serum HBV DNA level < 2000 IU/mL at the third month of therapy may be predictors of SVR.

scholarly journals Genome-wide Association Study Identifies Genetic Variants Associated With Early and Sustained Response to (Pegylated) Interferon in Chronic Hepatitis B Patients: The GIANT-B Study

2019 ◽  
Vol 69 (11) ◽  
pp. 1969-1979
Author(s):  
Willem P Brouwer ◽  
Henry L Y Chan ◽  
Pietro Lampertico ◽  
Jinlin Hou ◽  
Pisit Tangkijvanich ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Association Study ◽  
Chronic Hepatitis B ◽  
Genetic Variants ◽  
Genome Wide Association Study ◽  
Pegylated Interferon ◽  
Hbv Dna ◽  
Genome Wide Association ◽  
Genome Wide

AbstractBackground(Pegylated) Interferon ([Peg]IFN) therapy leads to response in a minority of chronic hepatitis B (CHB) patients. Host genetic determinants of response are therefore in demand.MethodsIn this genome-wide association study (GWAS), CHB patients, treated with (Peg)IFN for at least 12 weeks ± nucleos(t)ide analogues within randomized trials or as standard of care, were recruited at 21 centers from Europe, Asia, and North America. Response at 24 weeks after (Peg)IFN treatment was defined as combined hepatitis B e antigen (HBeAg) loss with hepatitis B virus (HBV) DNA <2000 IU/mL, or an HBV DNA <2000 IU/mL for HBeAg-negative patients.ResultsOf 1144 patients, 1058 (92%) patients were included in the GWAS analysis. In total, 282 (31%) patients achieved the response and 4% hepatitis B surface antigen (HBsAg) loss. GWAS analysis stratified by HBeAg status, adjusted for age, sex, and the 4 ancestry components identified PRELID2 rs371991 (B= −0.74, standard error [SE] = 0.16, P = 3.44 ×10–6) for HBeAg-positive patients. Importantly, PRELID2 was cross-validated for long-term response in HBeAg-negative patients. G3BP2 rs3821977 (B = 1.13, SE = 0.24, P = 2.46 × 10–6) was associated with response in HBeAg-negative patients. G3BP2 has a role in the interferon pathway and was further examined in peripheral blood mononuclear cells of healthy controls stimulated with IFNα and TLR8. After stimulation, less production of IP-10 and interleukin (IL)-10 proteins and more production of IL-8 were observed with the G3BP2 G-allele.ConclusionsAlthough no genome-wide significant hits were found, the current GWAS identified genetic variants associated with (Peg)IFN response in CHB. The current findings could pave the way for gene polymorphism-guided clinical counseling, both in the setting of (Peg)IFN and the natural history, and possibly for new immune-modulating therapies.Clinical Trials RegistationNCT01401400.

scholarly journals Serum miR-192-5p Levels Predict the Efficacy of Pegylated Interferon Therapy for Chronic Hepatitis B

2021 ◽  
Author(s):  
Yoshihito Nagura ◽  
Kentaro Matsuura ◽  
Etsuko Iio ◽  
Koji Fujita ◽  
Takako Inoue ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Multivariate Logistic Regression Analysis ◽  
Pegylated Interferon ◽  
Hbv Dna ◽  
Multivariate Logistic Regression ◽  
Hepatitis B E Antigen ◽  
End Of Treatment

Abstract We examined the association between serum miRNA (-192-5p, -122-3p, -320a and − 6126-5p) levels and the efficacy of pegylated interferon (Peg-IFN) monotherapy for chronic hepatitis B (CHB) patients. We enrolled 61 CHB patients treated with Peg-IFNα-2a weekly for 48 weeks, of whom 12 had a virological response (VR) and 49 did not VR (non-VR). A VR was defined as HBV DNA < 2,000 IU/ml, hepatitis B e antigen (HBeAg)-negative, and nucleos(t)ide analogue free at 48 weeks after the end of treatment. The non-VR group showed a significantly higher HBeAg-positivity rate, ALT, HBV DNA, and serum miR-192-5p levels at baseline (P = 0.024, P = 0.020, P = 0.007, P = 0.021, respectively). Serum miR-192-5p levels at 24 weeks after the start of treatment were also significantly higher in the non-VR than the VR group (P = 0.011). Multivariate logistic regression analysis for predicting VR showed that miR-192-5p level at baseline was an independent factor. Serum miR-192-5p levels were significantly correlated with the levels of HBV DNA, hepatitis B core-related antigen, and hepatitis B surface antigen (r = 0.484, 0.384 and 0.759, respectively). The serum miR-192-5p level was useful as a biomarker for the therapeutic efficacy of Peg-IFN in CHB treatment.

scholarly journals Efficacy of Different Nucleoside Analog Rescue Therapies for Entecavir-Resistant Chronic Hepatitis B Patients

2020 ◽  
Author(s):  
Jin Shang ◽  
Juan Zhou ◽  
Huan Liu ◽  
You Tu ◽  
Jinqiu Ran ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Combination Therapy ◽  
Chronic Hepatitis B ◽  
Therapy Group ◽  
Virologic Response ◽  
Hbv Dna ◽  
Combination Therapy Group ◽  
Clinical Issue ◽  
Significant Difference

Abstract Background Entecavir (ETV) is recommended as a first-line anti-HBV treatment. However, many chronic hepatitis B patients initiate anti-HBV treatment such as lamivudine and telbivudine with low genetic barriers in China, which leads to compensatory mutations and increases the rate of ETV resistance. The management of ETV resistance in China is an essential clinical issue. Methods Patients from 2011 to 2017 with nucleos(t)ide analog resistance were screened and 72 patients with ETV resistance were included. These patients received different rescue therapies including an ETV and adefovir (ADV) combination therapy group (n = 25), a tenofovir (TDF) monotherapy group (n = 27), and an ETV and TDF combination therapy group (n = 20). Virologic, biochemical, and serologic responses were compared among the three groups. Results The rate of ETV resistance increased form 6.04% in 2011 to 15.02% in 2017. Regarding the rates of negative HBV DNA at 48 weeks, no significant differences occurred in the TDF monotherapy and TDF combination groups (74.07% vs 70.00%), while the ETV and ADV group showed the worst virologic response (28.00%). TDF monotherapy and TDF combination therapy showed similar decline of HBV DNA at weeks 12, 24, and 48. There was no significant difference in the rates of HBeAg clearance, ALT normalization, and abnormal renal function between the three groups. Conclusions TDF monotherapy showed a comparable virologic response to TDF and ETV combination therapy and a better virologic response than ETV and ADV combination therapy. Thus, TDF monotherapy is the preferred rescue therapy for ETV resistance.

scholarly journals Comparison of Serum Hepatitis B Virus RNA Levels and Quasispecies Evolution Patterns between Entecavir and Pegylated-Interferon Mono-treatment in Chronic Hepatitis B Patients

2020 ◽  
Vol 58 (9) ◽  
Author(s):  
Xiao-qi Yu ◽  
Ming-jie Wang ◽  
De-min Yu ◽  
Pei-zhan Chen ◽  
Ming-yu Zhu ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Hbeag Seroconversion ◽  
Pegylated Interferon ◽  
Hbv Dna ◽  
Interferon Treatment ◽  
B Virus ◽  
Quasispecies Evolution ◽  
Rna Levels

ABSTRACT Hepatitis B virus (HBV) RNA may independently predict virological and serological response. This study aimed to compare dynamic changes in serum HBV RNA levels and HBV quasispecies evolution patterns between entecavir and pegylated-interferon mono-treatment in chronic hepatitis B patients and to determine the clinical significance during treatment. TaqMan real-time PCR was used for quantitative analysis. HBV RNA levels were retrospectively determined in serial serum samples from 178 chronic hepatitis B patients who received either entecavir or pegylated-interferon treatment. Both serum HBV DNA and RNA quasispecies were analyzed via next-generation sequencing. Receiver operating characteristics (ROC) analysis was performed to evaluate the prediction value of individual biomarkers for hepatitis B e antigen (HBeAg) seroconversion. Patients who received pegylated-interferon treatment showed stronger declines in HBV RNA levels than did those who received entecavir treatment. Serum HBV RNA levels were lower in patients with subsequent HBeAg seroconversion. At baseline, the level of HBV RNA was better than other indicators in predicting HBeAg seroconversion. Moreover, the predictive value of serum HBV RNA levels was better in the entecavir group. Baseline HBV RNA exhibited a significantly higher genetic diversity than HBV DNA and had a significant decline after 4 weeks of entecavir treatment. Higher baseline genetic diversity may result in a better outcome in pegylated-interferon-treated patients. Serum HBV RNA levels showed different decline kinetics, and HBV RNA quasispecies showed different evolution patterns in entecavir and pegylated-interferon mono-treatment. Taken together, serum HBV RNA may serve as a promising biomarker of HBeAg seroconversion in patients during antiviral treatment.

scholarly journals Whole exome HBV DNA integration is independent of the intrahepatic HBV reservoir in HBeAg-negative chronic hepatitis B

Gut ◽  
2020 ◽  
pp. gutjnl-2020-323300
Author(s):  
Valentina Svicher ◽  
Romina Salpini ◽  
Lorenzo Piermatteo ◽  
Luca Carioti ◽  
Arianna Battisti ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Hbv Dna ◽  
Dna Integration ◽  
Whole Exome ◽  
Number Of Patients ◽  
Hbv Dna Integration ◽  
Intrahepatic Hbv ◽  
Negative Chronic Hepatitis

ObjectiveThe involvement of HBV DNA integration in promoting hepatocarcinogenesis and the extent to which the intrahepatic HBV reservoir modulates liver disease progression remains poorly understood. We examined the intrahepatic HBV reservoir, the occurrence of HBV DNA integration and its impact on the hepatocyte transcriptome in hepatitis B ‘e’ antigen (HBeAg)-negative chronic hepatitis B (CHB).DesignLiver tissue from 84 HBeAg-negative patients with CHB with low (n=12), moderate (n=25) and high (n=47) serum HBV DNA was analysed. Covalently closed circular DNA (cccDNA), pregenomic RNA (pgRNA) were evaluated by quantitative PCR, whole exome and transcriptome sequencing was performed by Illumina, and the burden of HBV DNA integrations was evaluated by digital droplet PCR.ResultsPatients with low and moderate serum HBV DNA displayed comparable intrahepatic cccDNA and pgRNA, significantly lower than in patients with high HBV DNA, while hepatitis B core-related antigen correlated strongly with the intrahepatic HBV reservoir, reflecting cccDNA quantity. Whole exome integration was detected in a significant number of patients (55.6%, 14.3% and 25% in high, moderate and low viraemic patients, respectively), at a frequency ranging from 0.5 to 157 integrations/1000 hepatocytes. Hepatitis B surface antigen >5000 IU/mL predicted integration within the exome and these integrations localised in genes involved in hepatocarcinogenesis, regulation of lipid/drug metabolism and antiviral/inflammatory responses. Transcript levels of specific genes, including the proto-oncogene hRAS, were higher in patients with HBV DNA integration, supporting an underlying oncogenic risk in patients with low-level to moderate-level viraemia.ConclusionsHBV DNA integration occurs across all HBeAg-negative patients with CHB, including those with a limited HBV reservoir; localising in genes involved in carcinogenesis and altering the hepatocyte transcriptome.

scholarly journals Pretreatment serum HBsAg-to-HBV DNA ratio predicts a virologic response to entecavir in chronic hepatitis B

2011 ◽  
Vol 17 (4) ◽  
pp. 268 ◽  
Author(s):  
Joon Chang Song ◽  
Bo Young Min ◽  
Jin-Wook Kim ◽  
Jong Yeop Kim ◽  
Yeo Myeong Kim ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Virologic Response ◽  
Hbv Dna ◽  
Serum Hbsag ◽  
Pretreatment Serum

scholarly journals Efficacy of Different Nucleoside Analog Rescue Therapies for Entecavir-Resistant Chronic Hepatitis B Patients

2020 ◽  
Author(s):  
Jin Shang ◽  
Juan Zhou ◽  
Huan Liu ◽  
You Tu ◽  
Jinqiu Ran ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Combination Therapy ◽  
Chronic Hepatitis B ◽  
Therapy Group ◽  
Virologic Response ◽  
Hbv Dna ◽  
Combination Therapy Group ◽  
Clinical Issue ◽  
Significant Difference

Abstract Background: Entecavir (ETV) is recommended as a first-line anti-HBV treatment. However, many chronic hepatitis B patients initiate anti-HBV treatment such as lamivudine and telbivudine with low genetic barriers in China, which leads to compensatory mutations and increases the rate of ETV resistance. The management of ETV resistance in China is an essential clinical issue. Methods: Patients from 2011 to 2017 with nucleos(t)ide analog resistance were screened and 72 patients with ETV resistance were included. These patients received different rescue therapies including an ETV and adefovir (ADV) combination therapy group (n = 25), a tenofovir (TDF) monotherapy group (n = 27), and an ETV and TDF combination therapy group (n = 20). Virologic, biochemical, and serologic responses were compared among the three groups.Results: The rate of ETV resistance increased form 6.04% in 2011 to 15.02% in 2017. Regarding the rates of negative HBV DNA at 48 weeks, no significant differences occurred in the TDF monotherapy and TDF combination groups (74.07% vs 70.00%), while the ETV and ADV group showed the worst virologic response (28.00%). TDF monotherapy and TDF combination therapy showed similar decline of HBV DNA at weeks 12, 24, and 48. There was no significant difference in the rates of HBeAg clearance, ALT normalization, and abnormal renal function between the three groups. Conclusions: TDF monotherapy showed a comparable virologic response to TDF and ETV combination therapy and a better virologic response than ETV and ADV combination therapy. Thus, TDF monotherapy is the preferred rescue therapy for ETV resistance.

scholarly journals Prediction of the Response to Pegylated Interferon α-2a in Patients with HBeAg Positive Chronic Hepatitis B through Decline of Serum HBV DNA and Hepatitis B Virus Surface Antigen at Week 4

2012 ◽  
Vol 1 (4) ◽  
pp. 183-190
Author(s):  
Jian-ming Zheng ◽  
Ming-quan Chen ◽  
Meng-qi Zhu ◽  
Ning Li ◽  
Qian Li ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Surface Antigen ◽  
Pegylated Interferon ◽  
Hbv Dna ◽  
Interferon Α ◽  
Virus Surface ◽  
Hbsag Level ◽  
Positive Chronic Hepatitis

Abstract Objective To assess on-treatment serum HBsAg and HBV DNA kinetics in HBeAg-positive CHB patients to predict the efficacy of pegylated interferon (PEG-IFN) in early phase of treatment. Methods Forty-one treatment-naive HBeAg-positive patients treated with PEG-IFNα 2a at a dose of 180 μg/week for at least 24 weeks were evaluated. Their treatment response was assessed, including normalization of serum ALT, decline of serum HBV DNA and loss of HBeAg. Results We found that a decrease of HBV DNA level at the 4th week was positively correlated with the decrease of HBV DNA level at the 12th week and 24th week (r = 0.8202, P < 0.0001 and r = 0.6838, P < 0.0001, respectively). We observed that a decrease of HBsAg level at the 4th week was positively correlated with decrease of HBsAg level at the 12th week and 24th week (r = 0.4868, P = 0.0023 and r = 0.4251, P = 0.0109, respectively). A decrease of HBsAg level at the 24th week was positively correlated with the decrease of HBV DNA level at the 24th week (r = 0.5262, P = 0.0024). Serum level of IFN and IFN neutralizing antibody had no relationship with HBV DNA or HBsAg titers kinetics. Conclusions The decline of serum HBV DNA and hepatitis B surface antigen at the 4th week can be used to predict the response to PEG-IFNα 2a in patients with HBeAg positive chronic hepatitis B.

scholarly journals Efficacy of different nucleoside analog rescue therapies for entecavir-resistant chronic hepatitis B patients

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jin Shang ◽  
Juan Zhou ◽  
Huan Liu ◽  
Rili M. Ise ◽  
You Tu ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Combination Therapy ◽  
Chronic Hepatitis B ◽  
Therapy Group ◽  
Virologic Response ◽  
Hbv Dna ◽  
Combination Therapy Group ◽  
Clinical Issue ◽  
Significant Difference

Abstract Background Entecavir (ETV) is recommended as a first-line anti-HBV treatment. However, many chronic hepatitis B patients initiate anti-HBV treatment such as lamivudine and telbivudine with low genetic barriers in China, which leads to compensatory mutations and increases the rate of ETV resistance. The management of ETV resistance in China is an essential clinical issue. Methods Patients from 2011 to 2017 with nucleos(t)ide analog resistance were screened and 72 patients with ETV resistance were included. These patients received different rescue therapies including an ETV and adefovir (ADV) combination therapy group (n = 25), a tenofovir (TDF) monotherapy group (n = 27), and an ETV and TDF combination therapy group (n = 20). Virologic, biochemical, and serologic responses were compared among the three groups. Results The rate of ETV resistance among all HBV-resistant variants increased from 6.04% in 2011 to 15.02% in 2017. TDF monotherapy and TDF combination groups showed similar rates of negative HBV DNA at 48 weeks (74.07% vs 70.00%, P > 0.05), while the ETV and ADV group showed the worst virologic response (28.00%). Also, TDF monotherapy and TDF combination therapy showed similar decline of HBV DNA at weeks 12, 24, and 48. There was no significant difference in the rates of HBeAg clearance, ALT normalization, and abnormal renal function among the three groups. Conclusions TDF monotherapy showed a comparable virologic response to TDF and ETV combination therapy and a better virologic response than ETV and ADV combination therapy. Thus, TDF monotherapy is the preferred rescue therapy for ETV resistance.

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