Viral Biomarkers in Chronic HBeAg Negative HBV Infection

Hadziyannis, Emilia; Laras, Andreas

doi:10.3390/genes9100469

Cited by 53 publications

(40 citation statements)

References 136 publications

(154 reference statements)

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“…Sustained off‐treatment viral suppression is a well‐accepted clinical end‐point of antiviral therapy in patients with CHB. At present, baseline parameters have not been fully established to predict positive or negative outcomes in patients with HBeAg‐negative CHB treated with PEG‐IFN . In this report, our cohort with longitudinal follow‐up demonstrated that low baseline HBV RNA level was associated with response to PEG‐IFN‐based therapy.…”

Section: Discussionmentioning

confidence: 61%

Baseline and kinetics of serum hepatitis B virus RNA predict response to pegylated interferon‐based therapy in patients with hepatitis B e antigen‐negative chronic hepatitis B

Limothai

Chuaypen

Poovorawan

et al. 2019

Journal of Viral Hepatitis

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Serum hepatitis B virus (HBV) RNA has emerged as a novel biomarker of treatment response. This study aimed to investigate the role of this marker in predicting long-term outcome of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) receiving pegylated interferon (PEG-IFN)-based therapy. Serial serum samples from 91 patients with HBeAg-negative CHB previously treated with PEG-IFN alone or combined with entecavir in a randomized trial were retrospectively analysed. HBV RNA quantification was examined by droplet digital PCR. At the end of 3 years post-treatment follow-up, maintained virological response (MVR, HBV DNA < 2000 IU/mL), and hepatitis B surface antigen (HBsAg) clearance wereachieved in 37.4% (34/91) and 7.7% (7/91), respectively. Baseline serum HBV RNA concentrations correlated with HBV DNA and covalently closed circular DNA but did not correlate with HBsAg levels. Multiple regression analysis showed that pre-treatment HBV RNA and HBsAg were independently associated with MVR and HBsAg clearance. Baseline HBV RNA (cut-off 2.0 log 10 copies/mL) had a positive predictive value (PPV) and a negative predictive value in predicting MVR of 80.8% and 80.0%, respectively. At the same cut-off value, PPV and NPV for predicting HBsAg clearance were 30.8% and 95.4%, respectively. At week 12 during therapy, HBV RNA level ≥ 2 log 10 copies/mL displayed high NPVs of achieving MVR and HBsAg clearance (95% and 100%, respectively). In conclusion, the measurement of HBV RNA prior to PEG-IFN-based therapy could identify patients with high probability of MVR. In addition, HBV RNA kinetics may serve as a promising "stopping rule" in patients infected with HBV genotypes B or C. K E Y W O R D S cccDNA, chronic hepatitis B, entecavir, HBsAg, HBV RNA, pegylated interferon, stopping rule, virological response How to cite this article: Limothai U, Chuaypen N, Poovorawan K, et al. Baseline and kinetics of serum hepatitis B virus RNA predict response to pegylated interferon-based therapy in patients with hepatitis B e antigen-negative chronic hepatitis B.

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Section: Discussionmentioning

confidence: 61%

Baseline and kinetics of serum hepatitis B virus RNA predict response to pegylated interferon‐based therapy in patients with hepatitis B e antigen‐negative chronic hepatitis B

Limothai

Chuaypen

Poovorawan

et al. 2019

Journal of Viral Hepatitis

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“…31 All three proteins share an identical 149 amino acid sequence. 31,32 HBcAg, p22cr, and HBeAg can all be measured as HBcrAg by serological testing. 33,34…”

Section: Components Of Hbcrag (Fig 2)mentioning

confidence: 99%

“…p22cr is a 22-kDa precore protein present in HBV DNA-negative empty Dane-like particles [ 31 ]. All three proteins share an identical 149 amino acid sequence [ 31 , 32 ]. HBcAg, p22cr, and HBeAg can all be measured as HBcrAg by serological testing [ 33 , 34 ].…”

Section: Surrogate Marker Of Intrahepatic Hbv Replication: Hbcragmentioning

confidence: 99%

Novel biomarkers for the management of chronic hepatitis B

Inoue

2020

Clin Mol Hepatol

105

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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 <i>Lens culinaris</i> 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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“…The HBV surface protein is a very sensitive biomarker for viral infection, given that it is expressed at high levels in all viral infection phases [ 16 ]. In addition to its location in the viral envelope, the surface protein is secreted outside cells through vesicle-mediated exocytosis to form filamentous and spherical SVPs that lack a genome-containing capsid; therefore, the HBV surface protein is a relatively stable biomarker indicating an infection history [ 17 ].…”

Section: Hbv Surface Proteinsmentioning

confidence: 99%

Association of the Hepatitis B Virus Large Surface Protein with Viral Infectivity and Endoplasmic Reticulum Stress-mediated Liver Carcinogenesis

Lin

Hung

Huang

2020

Cells

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Hepatitis B is the most prevalent viral hepatitis worldwide, affecting approximately one-third of the world’s population. Among HBV factors, the surface protein is the most sensitive biomarker for viral infection, given that it is expressed at high levels in all viral infection phases. The large HBV surface protein (LHBs) contains the integral pre-S1 domain, which binds to the HBV receptor sodium taurocholate co transporting polypeptide on the hepatocyte to facilitate viral entry. The accumulation of viral LHBs and its prevalent pre-S mutants in chronic HBV carriers triggers a sustained endoplasmic reticulum (ER) overload response, leading to ER stress-mediated cell proliferation, metabolic switching and genomic instability, which are associated with pro-oncogenic effects. Ground glass hepatocytes identified in HBV-related hepatocellular carcinoma (HCC) patients harbor pre-S deletion variants that largely accumulate in the ER lumen due to mutation-induced protein misfolding and are associated with increased risks of cancer recurrence and metastasis. Moreover, in contrast to the major HBs, which is decreased in tumors to a greater extent than it is in peritumorous regions, LHBs is continuously expressed during tumorigenesis, indicating that LHBs serves as a promising biomarker for HCC in people with CHB. Continuing efforts to delineate the molecular mechanisms by which LHBs regulates pathological changes in CHB patients are important for establishing a correlation between LHBs biomarkers and HCC development.

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Viral Biomarkers in Chronic HBeAg Negative HBV Infection

Cited by 53 publications

References 136 publications

Baseline and kinetics of serum hepatitis B virus RNA predict response to pegylated interferon‐based therapy in patients with hepatitis B e antigen‐negative chronic hepatitis B

Baseline and kinetics of serum hepatitis B virus RNA predict response to pegylated interferon‐based therapy in patients with hepatitis B e antigen‐negative chronic hepatitis B

Novel biomarkers for the management of chronic hepatitis B

Association of the Hepatitis B Virus Large Surface Protein with Viral Infectivity and Endoplasmic Reticulum Stress-mediated Liver Carcinogenesis

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