Quantification of HBsAg in nucleos(t)ide-naïve patients treated for chronic hepatitis B with entecavir with or without tenofovir in the BE-LOW study

Zoulim, Fabien; Carosi, Giampiero; Greenbloom, Susan; Mazur, Włodzimierz; Nguyen, Tuan; Jeffers, Lennox J.; Brunetto, Maurizia Rossana; Yu, Song; Llamoso, Cyril

doi:10.1016/j.jhep.2014.08.031

Cited by 63 publications

(53 citation statements)

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“…Compared with serum HBV RNA levels, serum HBsAg levels correlated well with intrahepatic cccDNA levels at 96 weeks after NUC therapy (r ϭ 0.39, P Ͻ 0.01). Previous studies also identified a role of serum HBsAg in predicting treatment response during NUC therapy, and a higher HBsAg level at the end of NUC treatment was an independent predictor for posttreatment HBV relapse (18)(19)(20), which strongly supported our results indicating that serum HBsAg levels correlated well with intrahepatic cccDNA levels and that the levels might reflect the activity of cccDNA after NUC treatment.…”

Section: Discussionsupporting

confidence: 91%

Serum Hepatitis B Virus DNA, RNA, and HBsAg: Which Correlated Better with Intrahepatic Covalently Closed Circular DNA before and after Nucleos(t)ide Analogue Treatment?

Gao

Meng

et al. 2017

J Clin Microbiol

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The study was designed to investigate whether serum hepatitis B virus (HBV) RNA is a strong surrogate marker for intrahepatic HBV covalently closed circular DNA (cccDNA) compared with serum HBV DNA, hepatitis B surface antigen (HBsAg), and hepatitis B e antigen (HBeAg) in HBeAg-positive chronic hepatitis B (CHB) patients. Serum HBV RNA, HBV DNA, HBsAg, HBeAg, and intrahepatic cccDNA were quantitatively detected at baseline (n ϭ 82) and 96 weeks (n ϭ 62) after treatment with nucleos(t)ide analogue (NUC) in HBeAg-positive CHB patients. The correlations among serum HBV RNA, HBV DNA, HBsAg, HBeAg, and intrahepatic cccDNA levels were then statistically analyzed. The results showed that pretreatment intrahepatic cccDNA levels correlated better with serum HBV DNA levels (r ϭ 0.36, P Ͻ 0.01) than with serum HBV RNA levels (r ϭ 0.25, P ϭ 0.02), whereas no correlations were found between pretreatment intrahepatic cccDNA levels and HBsAg (r ϭ 0.15, P ϭ 0.17) or HBeAg (r ϭ 0.07, P ϭ 0.56) levels. At 96 weeks after NUC treatment, intrahepatic cccDNA levels correlated well with HBsAg levels (r ϭ 0.39, P Ͻ 0.01) but not with serum HBV RNA, HBV DNA, and HBeAg levels (all P Ͼ 0.05). Besides, the decline in the intrahepatic cccDNA level from baseline to week 96 correlated better with the reduction in the serum HBsAg levels than with the decreases in the levels of the other markers (for the HBsAg decline, r ϭ 0.38, P Ͻ 0.01; for the HBV DNA decline, r ϭ 0.35, P ϭ 0.01; for the HBV RNA decline, r ϭ 0.28, P Ͻ 0.05; for the HBeAg decline, r ϭ 0.18, P ϭ 0.19). In conclusion, the baseline serum HBV RNA level or its decline after 96 weeks of NUC therapy correlated with the corresponding intrahepatic cccDNA level, while it was less than that seen with serum HBV DNA at baseline and HBsAg (or its decline) at 96 weeks after treatment, respectively. KEYWORDS chronic hepatitis B, covalently closed circular DNA, HBV DNA, HBV RNA, hepatitis B surface antigen, nucleos(t)ide analogue H epatitis B virus (HBV) infection is a global health problem; an estimated 240 million persons are chronically infected, and about 650,000 people die annually due to chronic hepatitis B (CHB) worldwide (1). Though the currently available antiviral drugs can effectively reduce HBV DNA levels in serum of CHB patients, HBV may not be eliminated due to the persistence of HBV covalently closed circular DNA (cccDNA) in the infected hepatocytes, which represents the key HBV replicative intermediate (2). The fundamental role of intrahepatic cccDNA is as a template for transcription of all viral RNAs, including pregenomic RNA (pgRNA), which further produces the offspring virion

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Section: Discussionsupporting

confidence: 91%

Serum Hepatitis B Virus DNA, RNA, and HBsAg: Which Correlated Better with Intrahepatic Covalently Closed Circular DNA before and after Nucleos(t)ide Analogue Treatment?

Gao

Meng

et al. 2017

J Clin Microbiol

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“…38 The effect of NA in decreasing HBsAg levels was assessed by Zoulim et al, and they showed a decrease in HBsAg levels in NA-naïve patients receiving ETV (n = 182) with or without TDF (n = 197). 39 The range of the decrease in HBsAg levels between baseline and 96 weeks of ETV treatment was larger among HBeAg-positive patients than HBeAg-negative patients (0.91 IU/mL vs 0.13 logIU/mL). Furthermore, in the assessment according to HBV genotype, the range of the decrease in HBsAg levels in HBeAg-positive patients was the largest among genotype A rather than genotype B, C, or D (1.83, 0.76, 0.26, and 0.46 logIU/mL, respectively), while in HBeAg-negative patients, the decrease in HBsAg levels was rarely different between HBV genotypes (0.24, 0.28, 0.18, and 0.02 logIU/mL, respectively).…”

Section: Impact Of Nucleos(t)ide Analogue For Hccmentioning

confidence: 83%

The suppressive effect of nucleos(t)ide analogue treatment on the incidence of hepatocellular carcinoma in chronic hepatitis B patients

Hiramatsu

Yamada

Takehara

2016

J of Gastro and Hepatol

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The development of nucleos(t)ide analogues (NA) has influenced hepatitis B virus management. However, the annual incidence rate during NA treatment has been reported to be 0.3-1.2% in non-cirrhosis cases and 1.8-6.0% in cirrhosis cases, indicating that the suppressive effect of NA treatment on hepatocellular carcinoma (HCC) would be insufficient. Past studies, including one randomized control trial that compared lamivudine treatment with placebo, have revealed that NA treatment could suppress the incidence of HCC in patients with advanced fibrosis. However, it remains unknown whether NA treatment can suppress the incidence of HCC in chronic hepatitis patients without advanced fibrosis. The HCC incidence in patients treated with entecavir was similar to that of those treated with lamivudine, although entecavir exhibits a stronger viral suppression than lamivudine. The following risk factors related to the incidence of HCC during NA treatment have been identified: older age, male gender, pre-existing cirrhosis, a family clustering of hepatitis B virus, lower platelet counts, and higher hepatitis B core-related antigens as baseline factors and higher alpha fetoprotein levels as an on-treatment factor. Conversely, the loss of the hepatitis B surface antigen (HBsAg) by interferon or NA was correlated with a lower HCC incidence rate. Because interferon treatment has much more effects on reducing HBsAg levels compared with NA treatment, a combination treatment with NA and pegylated interferon can bring additional reduction of HBsAg levels compared with NA monotherapy. Further study is needed to clarify this.

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“…This combination did not provide added value in terms of HBsAg kinetics. 123 In a second double-blind study, HBeAg-positive treatment naïve patients with high HBV DNA and normal ALT levels were randomly assigned to either TDF plus placebo or a combination of TDF plus emtricitabine for 192 weeks. 124 At week 192, 55%…”

Section: Na Plus Na Recommendationsmentioning

confidence: 99%

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

Lampertico¹,

Agarwal²,

Berg³

et al. 2017

Journal of Hepatology

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Quantification of HBsAg in nucleos(t)ide-naïve patients treated for chronic hepatitis B with entecavir with or without tenofovir in the BE-LOW study

Cited by 63 publications

References 50 publications

Serum Hepatitis B Virus DNA, RNA, and HBsAg: Which Correlated Better with Intrahepatic Covalently Closed Circular DNA before and after Nucleos(t)ide Analogue Treatment?

Serum Hepatitis B Virus DNA, RNA, and HBsAg: Which Correlated Better with Intrahepatic Covalently Closed Circular DNA before and after Nucleos(t)ide Analogue Treatment?

The suppressive effect of nucleos(t)ide analogue treatment on the incidence of hepatocellular carcinoma in chronic hepatitis B patients

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

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