High Level of Hepatitis B Core–Related Antigen Associated With Increased Risk of Hepatocellular Carcinoma in Patients With Chronic HBV Infection of Intermediate Viral Load

Tseng, Tai‐Chung; Liu, Chun‐Jen; Hsu, Chin-Hsien; Hong, Chun‐Ming; Su, Tung‐Hung; Yang, Wanting; Chen, Chi‐Ling; Yang, Hung‐Chih; Huang, Yen‐Tsung; Kuo, Stephanie Fang–Tzu; Liu, Chen–Hua; Chen, Pei‐Jer; Chen, Ding‐Shinn

doi:10.1053/j.gastro.2019.08.028

Cited by 95 publications

(121 citation statements)

References 37 publications

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“…The HBV RNA level was higher at baseline in our HBeAg-positive patients with an HVL than that reported for HBeAg-positive patients in other studies. 5,14,23 This finding may be related to our selection of patients with an HVL. During NA treatment, the serum HBV RNA level of all patients decreased gradually from 0 to 48 weeks of therapy and was significantly lower than that at previous time points.…”

Section: Discussionmentioning

confidence: 89%

“…Recent evidence has suggested that CHB patients with an HVL are less likely to achieve a VR or HBeAg seroconversion and more likely to be associated with drugrelated resistance and treatment failure compared with CHB patients with a normal level. 13,14 At present, the value of using the HBV RNA level at different time points as a predictor of the VR or HBeAg seroconversion in HBeAgpositive CHB patients with an HVL at baseline is limited.…”

Section: Introductionmentioning

confidence: 99%

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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

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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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

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

Xia

Zhou

et al. 2020

IDR

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“…There are numerous clinical studies on the therapy of chronic hepatitis B, which tried to use HBcrAg instead of or in addition to HBV DNA for patient monitoring. A correlation of HBcrAg levels with the degree of liver fibrosis [35] and the development of hepatocellular carcinoma [36] was reported for HBeAg-negative patients. HBcrAg may be an acceptable substitute for HBV DNA for identification of patients requiring therapy [37], but monitoring of HBV DNA levels under antiviral therapy cannot adequately be done by HBcrAg in HBeAg-positive patients because nucleoside analogues do not suppress transcription of HBV DNA and the subsequent translation of HBeAg.…”

Section: Alternative Names For Hbv Antigens?mentioning

confidence: 93%

Peculiarities in the designations of hepatitis B virus genes, their products, and their antigenic specificities: a potential source of misunderstandings

et al. 2020

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The nomenclature of the hepatitis B virus (HBV) genes and their products has developed stepwise, occasionally in an erratic way, creating many misunderstandings, especially among those who do not know the structure of HBV and its genome in detail. One of the most frequent misunderstandings, even presented in leading journals, is the designation of HBV "e"-antigen as envelope or early antigen. Another problem area are the so-called "pre" regions in the HBV genome present upstream of both the core and the surface genes of HBV, inadvertently suggesting that they may be a part of corresponding precursor proteins. Misnomers and misclassifications are frequent in defining the subgenotypes and serological subtypes of HBV. Even the well-established terminology for HBV surface (HBs) or HBV core (HBc) antigen deviates from the conventional virological nomenclature for viral envelopes or capsid proteins/antigens, respectively. Another matter of undesirable variability between publications is the numbering of the nucleotides and the graphical representation of genomic maps. This editorial briefly explains how the nomenclature evolved, what it really means, and suggests how it could be adapted to today's knowledge.

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“…HBcrAg level of 4.0 log U/mL identified patients with an intermediate viral load who were at high risk for HCC. 65 For treatment-experienced patients, NA reduced, but did not eradicate, the risk of HCC occurrence. [59][60] Ando et al 59 reported that the cumulative incidence of HCC at 1, 3, and 5 years was 0.0%, 13.6%, and 17.7%, respectively in patients with serum HB-crAg levels ≥3.4 log U/mL at the time of HBV DNA disappearance and 0.0%, 0.0%, and 2.4%, respectively in patients with serum HBcrAg levels <3.4 log U/mL (P=0.005).…”

Section: Hbcrag In the Prediction Of Hcc Occurrence And Recurrencementioning

confidence: 99%

Novel biomarkers for the management of chronic hepatitis B

Inoue

2020

Clin Mol Hepatol

101

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Hepatitis B virus (HBV) cannot be eliminated completely from infected hepatocytes because of the presence of intrahepatic covalently closed circular DNA (cccDNA). As chronic hepatitis B (CHB) can progress to cirrhosis and hepatocellular carcinoma (HCC), it is important to manage CHB to prevent HCC development in high-risk patients with high viral replicative activity or advanced fibrosis. Serum biomarkers are noninvasive and valuable for the management of CHB. Hepatitis B core-related antigen (HBcrAg) correlates with serum HBV DNA and intrahepatic cccDNA. In CHB patients with undetectable serum HBV DNA or loss of HBsAg, HBcrAg still can be detected and the decrease in HBcrAg levels is significantly associated with hopeful outcomes. Therefore, HBcrAg can predict HCC occurrence or recurrence. Measurement of the Mac-2 binding protein glycosylation isomer (M2BPGi) has been introduced for the evaluation of liver fibrosis. Because elevated M2BPGi in CHB is related to liver fibrosis and the prediction of HCC development, monitoring its progression is essential. Because alpha fetoprotein (AFP) has insufficient sensitivity and specificity for early-stage HCC, a combination of AFP plus protein induced by vitamin K absence factor II, or AFP plus Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein might improve the diagnosis of HCC development. Additionally, Dickkopf-1 and circulating immunoglobulin G antibodies are the novel markers to diagnose HCC or assess HCC prognosis. This review provides an overview of novel HBV biomarkers used for the management of intrahepatic viral replicative activity, liver fibrosis, and HCC development.

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High Level of Hepatitis B Core–Related Antigen Associated With Increased Risk of Hepatocellular Carcinoma in Patients With Chronic HBV Infection of Intermediate Viral Load

Cited by 95 publications

References 37 publications

<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>

<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>

Peculiarities in the designations of hepatitis B virus genes, their products, and their antigenic specificities: a potential source of misunderstandings

Novel biomarkers for the management of chronic hepatitis B

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