Significance of hepatitis <scp>B</scp> virus core‐related antigen and covalently closed circular <scp>DNA</scp> levels as markers of hepatitis <scp>B</scp> virus re‐infection after liver transplantation

Matsuzaki, Takashi; Ichikawa, Tatsuki; Otani, M.; Akiyama, Motohisa; Ozawa, Eisuke; Miuma, Satoshi; Miyaaki, Hisamitsu; Taura, Naota; Hayashi, Tomayoshi; Okudaira, Sadayuki; Takatsuki, Mitsuhisa; Isomoto, Hajime; Takeshima, Fuminao; Eguchi, Susumu

doi:10.1111/jgh.12182

Cited by 39 publications

(47 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, it is plausible that all patients who seroconverted to anti‐HBsAg were exposed to HBsAg at some point during the follow‐up. This implies that these patients should have retained over time the capability to synthesize HBsAg and, hence, the presence of cccDNA in the hepatocyte nuclei, despite the repeated negative tissue assays at enrollment . Otherwise, antigen presenting T cells may have recruited HBsAg in extrahepatic loci.…”

Section: Discussionmentioning

confidence: 99%

Complete hepatitis B virus prophylaxis withdrawal in hepatitis B surface antigen–positive liver transplant recipients after longterm minimal immunosuppression

Lenci¹,

Baiocchi²,

Tariciotti³

et al. 2016

Liver Transpl

View full text Add to dashboard Cite

Tailored approaches have been attempted to prevent hepatitis B virus (HBV) reinfection in antibodies against hepatitis B surface antigen (HBsAg)-positive liver transplantation (LT) recipients in order to minimize the use of hepatitis B immune globulin (HBIG) and nucleoside analogues (NAs). We report the results of complete HBV prophylaxis withdrawal after a follow-up of at least 6 years in LT recipients with undetectable serum HBV DNA and intrahepatic total HBV DNA and covalently closed circular DNA at LT. We included 30 HBsAg positive, hepatitis B e antigen-negative recipients, 6 with hepatitis C virus and 7 with hepatitis D virus coinfection, who had received HBIG plus NA for at least 5 years after LT. Stepwise HBIG and NA withdrawal was performed in two 6-month periods under strict monitoring of HBV virology. All patients underwent a clinical, biochemical, and virological follow-up at 3-6 month intervals. HBV recurrence (HBsAg seroreversion ± detectable HBV DNA) occurred in 6 patients: in 1 patient after HBIG interruption and in 5 after both HBIG and NA cessation. Only 3 patients required reinstitution of HBV prophylaxis because of persistent HBV replication, and all achieved optimal control of HBV infection and did not experience clinical events. The other who recurred showed only short-lasting HBsAg positivity, with undetectable HBV DNA, followed by spontaneous anti-HBs seroconversion. An additional 15 patients mounted an anti-HBs titer, without previous serum HBsAg detectability. At the end of follow-up, 90% of patients were still prophylaxis-free, 93.3% were HBsAg negative, and 100% were HBV DNA negative; 60% had anti-HBs titers >10 IU/L (median, 143; range, 13-1000). This small series shows that complete prophylaxis withdrawal is safe in patients transplanted for HBV-related disease at low risk of recurrence and is often followed by spontaneous anti-HBs seroconversion. Further studies are needed to confirm this finding. Liver Transplantation 22 1205-1213 2016 AASLD.

show abstract

Section: Discussionmentioning

confidence: 99%

Complete hepatitis B virus prophylaxis withdrawal in hepatitis B surface antigen–positive liver transplant recipients after longterm minimal immunosuppression

Lenci¹,

Baiocchi²,

Tariciotti³

et al. 2016

Liver Transpl

View full text Add to dashboard Cite

show abstract

“…Furthermore, serum HBcrAg levels were correlated with CCC DNA levels and frequency of HBcAg (+) hepatocytes in the liver and with liver disease activity [87,89,92,93]. It was also found to predict liver cancer development and recurrence in HBV-infected patients, and was an even better predictor than serum HBV DNA [92,94].…”

Section: Potential Applications Of Hbv Particles In Clinical Managmentioning

confidence: 99%

Complete and Incomplete Hepatitis B Virus Particles: Formation, Function, and Application

Liu

2017

Viruses

239

245

View full text Add to dashboard Cite

Hepatitis B virus (HBV) is a para-retrovirus or retroid virus that contains a double-stranded DNA genome and replicates this DNA via reverse transcription of a RNA pregenome. Viral reverse transcription takes place within a capsid upon packaging of the RNA and the viral reverse transcriptase. A major characteristic of HBV replication is the selection of capsids containing the double-stranded DNA, but not those containing the RNA or the single-stranded DNA replication intermediate, for envelopment during virion secretion. The complete HBV virion particles thus contain an outer envelope, studded with viral envelope proteins, that encloses the capsid, which, in turn, encapsidates the double-stranded DNA genome. Furthermore, HBV morphogenesis is characterized by the release of subviral particles that are several orders of magnitude more abundant than the complete virions. One class of subviral particles are the classical surface antigen particles (Australian antigen) that contain only the viral envelope proteins, whereas the more recently discovered genome-free (empty) virions contain both the envelope and capsid but no genome. In addition, recent evidence suggests that low levels of RNA-containing particles may be released, after all. We will summarize what is currently known about how the complete and incomplete HBV particles are assembled. We will discuss briefly the functions of the subviral particles, which remain largely unknown. Finally, we will explore the utility of the subviral particles, particularly, the potential of empty virions and putative RNA virions as diagnostic markers and the potential of empty virons as a vaccine candidate.

show abstract

“…In recent years, quantitative HBsAg (qHBsAg) has been proven to have a better correlation with intrahepatic cccDNA than either HBV DNA or HBeAg. Besides, a new enzyme immunoassay that detects hepatitis B core-related antigen (HBcrAg) also has been reported to reflect intrahepatic cccDNA recently 7, 8 . According to reports in the literature, HBcrAg consists of HBcAg, HBeAg, and p22cr, which is a precore protein from amino acid −28 to at least amino acid 150, by coding the precore/core region 9 .…”

Section: Introductionmentioning

confidence: 99%

Serum hepatitis B core-related antigen is a satisfactory surrogate marker of intrahepatic covalently closed circular DNA in chronic hepatitis B

Chen

Feng

Wang

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Recently, hepatitis B core-related antigen (HBcrAg) has been suggested as an additional marker of hepatitis B virus (HBV) infection. This study aimed to investigate whether serum quantitative HBcrAg (qHBcrAg) was a satisfactory surrogate marker of intrahepatic covalently closed circular DNA (cccDNA). A total of 139 patients with liver biopsy were enrolled, consisting of 59 patients in immune tolerance (IT) phase, 52 patients in immune clearance (IC) phase, 18 patients in low-replication (LR) phase, and 10 patients in reactivation phase. All patients in IC phase have received entecavir (ETV) therapy, and 32 of them undergone a second liver biopsy at 24 months. Among those patients, qHBcrAg was strongly correlated with intrahepatic cccDNA, which is superior to that of qHBsAg and HBV DNA. And similar findings were also observed in patients in IT, IC, LR and reactivation phases. Among the 32 ETV-treated patients with a second liver biopsy in IC phase, the decline of intrahepatic cccDNA was accompanied by changes in both qHBcrAg and qHBsAg. However, as compared to qHBsAg, the change of qHBcrAg was more strongly associated with intrahepatic cccDNA-decline. In summary, serum qHBcrAg should be a satisfactory surrogate of intrahepatic HBV cccDNA in CHB patients.

show abstract

Significance of hepatitis B virus core‐related antigen and covalently closed circular DNA levels as markers of hepatitis B virus re‐infection after liver transplantation

Abstract: HBcrAg and cccDNA were useful as HBV re-infection markers after LT. Keeping patients' HBcrAg and cccDNA negative after LT might contribute to long-term graft survival.

Cited by 39 publications

References 19 publications

Complete hepatitis B virus prophylaxis withdrawal in hepatitis B surface antigen–positive liver transplant recipients after longterm minimal immunosuppression

Complete hepatitis B virus prophylaxis withdrawal in hepatitis B surface antigen–positive liver transplant recipients after longterm minimal immunosuppression

Complete and Incomplete Hepatitis B Virus Particles: Formation, Function, and Application

Serum hepatitis B core-related antigen is a satisfactory surrogate marker of intrahepatic covalently closed circular DNA in chronic hepatitis B

Contact Info

Product

Resources

About