Clinical evaluation of a new enzyme immunoassay for hepatitis B virus core‐related antigen; a marker distinct from viral DNA for monitoring lamivudine treatment

Rokuhara, Akinori; Tanaka, Eiji; Matsumoto, Akihiro; Kimura, Tetsunori; Yamaura, Takahiro; Orii, Koji; Sun, Xiaohong; Yagi, Shusuke; Maki, Norio; Kiyosawa, Kendo

doi:10.1046/j.1365-2893.2003.00437.x

Cited by 95 publications

(118 citation statements)

References 25 publications

(28 reference statements)

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“…p22cr is found in empty and HBV DNA negative virus particles; the production of empty particles is not dependent on the formation of HBV DNA [Kimura et al, 2005]. Several reports indicate that the concentration of serum HBcrAg is closely correlated with peripheral HBV DNA in untreated patients [Rokuhara et al, 2003;Tanaka et al, 2006]. Additionally, HBcrAg is considered as a prospective marker of the appearance of drug-resistant HBV mutants and of the identification of patients with low risk of HBV reactivation after discontinuation of lamivudine administration, while peripheral HBV DNA does not qualify as a prospective marker in these patients Shinkai et al, 2006;Tanaka et al, 2006;Matsumoto et al, 2007].…”

Section: Introductionmentioning

confidence: 98%

Correlation between serum hepatitis B virus core‐related antigen and intrahepatic covalently closed circular DNA in chronic hepatitis B patients

Suzuki

Miyakoshi

Kobayashi

et al. 2008

Journal of Medical Virology

166

187

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Nucleos(t)ide analogues are utilized for the treatment of chronic HBV infection, and HBe seroconversion and HBV DNA levels are commonly used as markers of viral status and as primary treatment endpoints. Recently, a new assay was prepared for the detection of serum HBV corerelated antigen (HBcrAg), consisting of HBcAg, HBeAg, and p22cr, which is a precore protein from amino acid À28 to at least amino acid 150, by coding the precore/core region. In this study, we examined the correlation between serum HBcrAg concentration and viral status by the analysis of serum HBeAg, HBsAg, peripheral HBV DNA, and intrahepatic covalently closed circular DNA (cccDNA) in 57 chronic hepatitis B patients. Intrahepatic cccDNA was detected in all 57 patients, 42 patients were HBcrAg-positive, and serum HBcrAg concentration level was closely correlated with cccDNA. Additionally, positive HBcrAg concentration level results were observed in 6 out of 13 HBsAg seroclearance patients and 20 out of 31 HBV DNA-negative patients. Moreover, the correlation between HBcrAg and cccDNA in these 31 HBV DNAnegative patients was statistically significant (r ¼ 0.482, P ¼ 0.006). These data suggest that serum HBcrAg concentration is well correlated with intrahepatic cccDNA level, and that the measurement of serum HBcrAg may be clinically useful for monitoring intrahepatic HBV viral status, especially in patients under treatment with nucleos(t)ide analogues.

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Section: Introductionmentioning

confidence: 98%

Correlation between serum hepatitis B virus core‐related antigen and intrahepatic covalently closed circular DNA in chronic hepatitis B patients

Suzuki

Miyakoshi

Kobayashi

et al. 2008

Journal of Medical Virology

166

187

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“…In this study, the rate of undetectable HBV DNA level and the normalization of ALT level at 1 year after the initiation of ETV treatment were similar to that of previous results. However, although an undetectable HBV DNA level and ALT level normalization are achieved with ETV treatment, complete elimination of intracellular HBV remains difficult [20,21]. It was reported that although ETV can considerably reduce the risk of HCC development [9], HCC development persists, and the details remain unclear.…”

Section: Discussionmentioning

confidence: 99%

Transient elastography is useful for evaluating hepatocellular carcinoma development during entecavir treatment of chronic hepatitis B virus infection

Shimada¹,

Iwase²,

Hirashima³

et al. 2017

Gastroenterol Hepatol Endosc

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Objective: Chronic hepatitis B virus (HBV) infection leads to cirrhosis and hepatocellular carcinoma (HCC). Entecavir (ETV) is effective for treating patients with HBV infection. However, the process of HCC development in patients treated with ETV remains unclear. We used transient elastography to investigate whether HCC development was correlated with liver stiffness (LS).Methods: This retrospective study enrolled 100 patients with chronic HBV infection who were treated with ETV from August 2007 to November 2015. The baseline patient characteristics were as follows: average age 54.8 ± 13.8 years, 64 men, 11 with cirrhosis, 32 positive for HBe antigen, median HBV DNA level 3.0 log copies/ mL, and treatment duration 55.0 ± 28.7 months. One year after the initiation of ETV treatment, laboratory data and viral markers were evaluated. LS values were measured using transient elastography.Results: HBV DNA became undetectable in 90 patients, and alanine aminotransferase (ALT) levels normalized in 86%. Alpha-fetoprotein levels decreased from 12.0 ± 35.7 to 3.2 ± 1.4 ng/mL (p < 0.05). HCC developed in seven patients. The cumulative incidence of HCC at 1, 3, and 5 years was 1%, 4%, and 6%, respectively. HCC development was not affected by HBV DNA negativity or by ALT level normalization. Patients who developed HCC had a higher rate of cirrhosis and higher LS values (≥ 6.8 kPa) than patients who did not develop HCC (cirrhosis: 57.1% vs. 7.5%, p < 0.001; LS values ≥ 6.8 kPa: 83.3% vs. 16.3%, p < 0.001). Conclusion: LS values can be useful for the evaluation of HCC development in patients with chronic HBV infection treated with ETV.

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“…The serum concentration of HBV core-related antigen was measured using the CLEIA reported previously [Kimura et al, 2002;Rokuhara et al, 2003]. In summary, 100 ml serum was mixed with 50 ml pretreatment solution containing 15% sodium dodecylsulfate and 2% Tween 60.…”

Section: Serological Markers For Hbvmentioning

confidence: 99%

“…A chemiluminescence enzyme immunoassay (CLEIA) was developed previously for the detection of HBV corerelated antigen [Kimura et al, 2002;Rokuhara et al, 2003]. The HBV core-related antigen is expressed on HBe and core (HBc) antigens; both proteins are transcribed from the precore/core gene and their first 149 amino acids are identical.…”

Section: Introductionmentioning

confidence: 99%

Patients with and without loss of hepatitis B virus DNA after hepatitis B e antigen seroconversion have different virological characteristics

Misawa

Matsumoto

Tanaka

et al. 2005

Journal of Medical Virology

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The characteristic differences between patients with and without loss of hepatitis B virus (HBV) DNA after achieving hepatitis B e antigen seroconversion were analyzed by comparing changes in HBV DNA and HBV core-related antigen levels during a period from 3 years before to 3 years after the seroconversion. Of the 24 seroconverters, 6 (inactive replication group) showed continuous loss of HBV DNA in serum after the seroconversion and the remaining 18 did not lose HBV DNA (active replication group). The HBV DNA level was similar between the two groups, while the HBV core-related antigen level was significantly lower in the active replication group than in the inactive replication group before the seroconversion. The levels of both HBV DNA and HBV core-related antigen decreased remarkably around the time of seroconversion in the inactive replication group, while these levels did not change or decreased slightly in the active replication group. After the seroconversion, the HBV DNA level was significantly higher in the active replication group than in the inactive replication group, while the HBV core-related antigen level was similarly low between the two groups. Because the serum level of HBV core-related antigen mainly reflects that of HBe antigen, the low level of HBV core-related antigen seen after seroconversion in both groups might have contributed to the occurrence of seroconversion. The precore and core promoter mutations which cause diminished excretion of hepatitis B e antigen were significantly more frequent in the active replication group than in the inactive replication group. It was therefore considered that the seroconversion was caused mainly by a decrease in viral replication in the inactive replication group, and mainly by a decrease in HBe antigen production in the active replication group.

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Clinical evaluation of a new enzyme immunoassay for hepatitis B virus core‐related antigen; a marker distinct from viral DNA for monitoring lamivudine treatment

Cited by 95 publications

References 25 publications

Correlation between serum hepatitis B virus core‐related antigen and intrahepatic covalently closed circular DNA in chronic hepatitis B patients

Correlation between serum hepatitis B virus core‐related antigen and intrahepatic covalently closed circular DNA in chronic hepatitis B patients

Transient elastography is useful for evaluating hepatocellular carcinoma development during entecavir treatment of chronic hepatitis B virus infection

Patients with and without loss of hepatitis B virus DNA after hepatitis B e antigen seroconversion have different virological characteristics

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