Association Between Negative Results From Tests for HBV DNA and RNA and Durability of Response After Discontinuation of Nucles(t)ide Analogue Therapy

Fan, Rong; Zhou, Bin; Xu, Min; Tan, Deming; Niu, Junqi; Wang, Hao; Ren, Hong; Chen, Xinyue; Wang, Maorong; Ning, Qin; Shi, Guangfeng; Sheng, Jifang; Tang, Hong; Bai, Xue–Fan; Shi, Liu; Lu, Fengmin; Peng, Jie; Sun, Jian; Xie, Qing; Hou, Jinlin; Wan, Mo-Bin; Chen, Shijun; Yu, Yan-yan; Ma, Hong; Cheng, Jun; Zhang, Hongfei; Liu, Huimin; Gao, Zhiliang; Dou, Xiaoguang

doi:10.1016/j.cgh.2019.07.046

Cited by 83 publications

(94 citation statements)

References 22 publications

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“…Serum HBV RNA was quantified using one step reverse transcription real‐time quantitative polymerase chain reaction (RT‐qPCR) with HBV specific primers (Forward: 5′‐GCG GGG TTT TTC TTG TTG AC‐3′ and reverse: 3′‐GCG ATA ACC AGG ACA AAT TG‐5′) using TaqMan probes, as described previously 22 . Negative results of qPCR carried out in parallel on DNase I‐treated RNA samples without a reverse transcription step (“no‐RT controls”) confirmed no HBV DNA contamination in RT‐qPCR.…”

Section: Methodsmentioning

confidence: 99%

Factors associated with the biphasic kinetics of serum HBV RNA in patients with HBeAg‐positive chronic hepatitis B treated with nucleos(t)ide analogues

Shi

Liu

et al. 2020

Aliment Pharmacol Ther

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Summary Background Serum hepatitis B virus (HBV) RNA is a novel biomarker for evaluating treatment response. Detailed information regarding serum HBV RNA kinetics during treatment with nucleos(t)ide analogues (NAs) is limited. Aims To ascertain serum HBV RNA kinetics during long‐term NA treatment and identify associated factors. Methods We enrolled 76 HBeAg‐positive chronic hepatitis B patients receiving NA from randomised controlled trials. Laboratory assays were undertaken every 3 months. Factors associated with serum HBV RNA kinetics were identified by generalised estimating equations. Results Baseline serum HBV RNA was 8.5 ± 1.0 log10 copies/mL. Decline in serum HBV RNA during NA therapy was biphasic: the first phase (HBV DNA detectable) had a fast decrease (median slope, −0.207 log10 copies/mL/month) and was followed by a second phase (HBV DNA undetectable) with slow decrease (median slope, −0.071 log10 copies/mL/month). In the first phase, factors independently associated with lower initial serum HBV RNA were male sex (OR, 0.685, P = 0.044), low baseline HBsAg (OR, 0.525, P = 0.001) and rapid virological response (RVR) (OR, 0.624, P = 0.031). In the second phase, only RVR was independently associated with serum HBV RNA kinetics, including its lower initial level (OR, 0.694, P = 0.043) and greater decline (OR, 0.966, P = 0.002). Based on viral dynamics, time needed to achieve undetectable serum HBV RNA from baseline was 43.56 (IQR: 29.49‐66.40) months. Conclusion RVR was a significant determinant for biphasic decline in serum HBV RNA during NA treatment, which significantly influenced the treatment duration required to achieve undetectable serum HBV RNA.

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Section: Methodsmentioning

confidence: 99%

Factors associated with the biphasic kinetics of serum HBV RNA in patients with HBeAg‐positive chronic hepatitis B treated with nucleos(t)ide analogues

Shi

Liu

et al. 2020

Aliment Pharmacol Ther

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“…Serum viral load, which is measured via serum HBV DNA quantification, has been assessed in various settings as a tool for treatment decisions in CHB patients, but in respect to patient management after NAs discontinuation, only few studies showed that there is association between higher pretreatment HBV DNA levels and post-NAs relapses [17,18,21,22,29,30,32] or HBsAg loss [14,33]. On the other hand, negative results were provided by a number of other cohorts that have examined the association between pretreatment serum HBV DNA levels and virological relapses [14,16,17,[23][24][25]44], clinical relapses [23,31,[33][34][35]44,45] or HBsAg loss [14,22,36,37,39].…”

Section: Hbv Dnamentioning

confidence: 99%

“…Serum HBV RNA levels, which seem to correlate with intrahepatic HBV cccDNA transcriptional activity [40], have been less studied in the setting of NAs discontinuation. It is suggested, though, that using HBV RNA levels in combination with HBV DNA levels can predict the risk of off-therapy relapses [49], whereas more recent data supported that undetectability of both serum HBV DNA and HBV RNA at EOT was associated with post NAs remission [45]. Yet, further research is needed to answer whether these promising markers may be used in clinical practice in this setting.…”

Section: Newer Hbv Virological Markersmentioning

confidence: 99%

Emerging Diagnostic Tools to Decide When to Discontinue Nucleos(t)ide Analogues in Chronic Hepatitis B

Papatheodoridi

Papatheodoridis

2020

Cells

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The aim of this review is to outline emerging biomarkers that can serve as diagnostic tools to identify non-cirrhotic chronic hepatitis B (CHB) patients who could safely discontinue nucleos(t)ide analogues (NAs) before HBsAg loss. Regarding possible predictors of post-NAs outcomes, a number of studies have evaluated numerous factors, which can be categorised in markers of hepatitis B virus (HBV) activity, markers of host immune response and markers of other patient characteristics. In clinical practice, the most important question for patients who discontinue NAs is to differentiate those who will benefit by achieving HBsAg loss or at least by remaining in remission and those who will relapse requiring retreatment. Most of the discontinuation studies so far came from Asian and only few from European populations and examined the rates and predictors of post-NA virological and/or combined relapses or HBsAg loss. To date, there is still controversy about predictors of post-NA relapses, while only HBsAg serum levels at NA discontinuation seem to be the most robust predictive marker of the probability of subsequent off-treatment HBsAg seroclearance. Newer viral markers such as HBV RNA and hepatitis B core-related antigen seem promising, but further research is required.

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“…Quantitative determination of HBV RNA was carried out according to the method of Fan and colleagues. 17 HBV RNA was isolated from 200 μL of serum using the QIAamp MinElute Virus Spin kit (Qiagen, Hilden, Germany) according to manufacturer instructions, and treated subsequently with DNase I (Thermo Fisher Scientific, Waltham, MA, USA). DNase I-digested HBV RNA was quantified by TaqMan probe-based one-step reverse transcription real-time quantitative polymerase chain reaction in a LightCycler ® 480 Instrument II system (Roche Diagnostics).…”

Section: Serologymentioning

confidence: 99%

<p>Serum Hepatitis B Virus RNA Levels Predict HBeAg Seroconversion and Virological Response in Chronic Hepatitis B Patients with High Viral Load Treated with Nucleos(t)ide Analog</p>

Xia

Zhou

et al. 2020

IDR

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Background and Aim: Hepatitis B virus (HBV) RNA has attracted increasing attention as a novel serum marker for intrahepatic HBV replication. However, the predictive value of the serum level of HBV RNA for hepatitis B e-antigen (HBeAg) seroconversion and viral response among patients with a high viral load (HVL) is unclear. We evaluated the role of the serum level of HBV RNA as a predictor of treatment response in chronic HBV (CHB) patients with an HVL. Patients and Methods: The study cohort was 66 HBeAg-positive CHB patients with an HVL (serum HBV DNA >1.9×10 6 IU/mL) at baseline from our previous prospective cohort study treated with lamivudine (LAM) and adefovir dipivoxil(ADV) (N=31) or entecavir alone (N=35) for ≤96 weeks. The serum HBV RNA level was quantified by TaqMan ® probebased reverse transcription real-time quantitative polymerase chain reaction at four time points. Results: The baseline serum HBV RNA level (in log 10 copies/mL) in patients treated with LAM+ADV and ETV monotherapy was 8.97±1.22 and 9.15±0.92, respectively. After nucleos(t)ide analog (NA) therapy, the serum HBV RNA level decreased steadily in all patients (week 0 vs week 12, p<0.001; week 12 vs week 24, p=0.010; week 24 vs week 48, p<0.001). Fifty-three (80.3%) patients achieved a virologic response (VR), and 12 (18.2%) achieved HBeAg seroconversion after 96 weeks. Multivariate analyses revealed that the serum HBV RNA level at week 12 could predict HBeAg seroconversion (OR 3.560, 95% CI: 1.39-9.110, p=0.008) and VR (1.908, 1.115-3.265, 0.018) at 96 weeks. Analyses of receiver operating characteristic curves indicated that the serum HBV RNA level 12 weeks after NA treatment had predictive value for HBeAg seroconversion (AUC=0.847, p<0.001) and VR (AUC=0.736, p=0.011). Conclusion: The serum level of HBV RNA at 12 weeks could predict HBeAg seroconversion and a VR during NA treatment in CHB patients with an HVL.

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Association Between Negative Results From Tests for HBV DNA and RNA and Durability of Response After Discontinuation of Nucles(t)ide Analogue Therapy

Cited by 83 publications

References 22 publications

Factors associated with the biphasic kinetics of serum HBV RNA in patients with HBeAg‐positive chronic hepatitis B treated with nucleos(t)ide analogues

Factors associated with the biphasic kinetics of serum HBV RNA in patients with HBeAg‐positive chronic hepatitis B treated with nucleos(t)ide analogues

Emerging Diagnostic Tools to Decide When to Discontinue Nucleos(t)ide Analogues in Chronic Hepatitis B

<p>Serum Hepatitis B Virus RNA Levels Predict HBeAg Seroconversion and Virological Response in Chronic Hepatitis B Patients with High Viral Load Treated with Nucleos(t)ide Analog</p>

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