Evidence map›Paper›PMID 41814529›Full record

Observational studyJournal of gastroenterology and hepatology2026

High Intrahepatic cccDNA in Resolved HBV Infection: Insights From Living Donor Liver Transplantation With Anti-HBc-Positive Grafts.

Sung Kwan Bae, Nobuhisa Akamatsu, Akihiko Ichida, Yujiro Nishioka, Yoshinori Inagaki, Nozomi Miyake, Takeshi Takamoto, Yoshikuni Kawaguchi, Sumihito Tamura, Junichi Arita and 6 more

Abstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Journal of gastroenterology and hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Sung Kwan BaeArtificial Organ and Transplantation Division, Department of Surgery, University of Tokyo, Tokyo, Japan.
Nobuhisa AkamatsuArtificial Organ and Transplantation Division, Department of Surgery, University of Tokyo, Tokyo, Japan.
Akihiko IchidaArtificial Organ and Transplantation Division, Department of Surgery, University of Tokyo, Tokyo, Japan.
Yujiro NishiokaArtificial Organ and Transplantation Division, Department of Surgery, University of Tokyo, Tokyo, Japan.
Yoshinori InagakiDepartment of Kampo Medicine, Yokohama University of Pharmacy, Yokohama, Kanagawa, Japan.
Nozomi MiyakeDepartment of Gastroenterology and Hepatology, Academic Fields of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Takeshi TakamotoArtificial Organ and Transplantation Division, Department of Surgery, University of Tokyo, Tokyo, Japan.
Yoshikuni KawaguchiArtificial Organ and Transplantation Division, Department of Surgery, University of Tokyo, Tokyo, Japan.
Sumihito TamuraArtificial Organ and Transplantation Division, Department of Surgery, University of Tokyo, Tokyo, Japan.
Junichi AritaDepartment of Gastroenterological Surgery, Akita University School of Medicine, Akita, Japan.
Junichi KanekoDepartment of Gastrointestinal Surgery, Hepato-Biliary-Pancreatic Surgery, Tokai University, Hachioji Hospital, Tokyo, Japan.
Motoyuki OtsukaDepartment of Gastroenterology and Hepatology, Academic Fields of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Yasuhito TanakaDepartment of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.ORCID https://orcid.org/0000-0002-2473-6966
Hiroshi YotsuyanagiJapan Institute for Health Security (JIHS), Tokyo, Japan.
Kyoji MoriyaDivision of Infection Control and Prevention, Education Research Center, Tokyo Healthcare University, Shinagawa, Japan.
Kiyoshi HasegawaArtificial Organ and Transplantation Division, Department of Surgery, University of Tokyo, Tokyo, Japan.ORCID https://orcid.org/0000-0001-8734-740X

Funding

Japan Agency for Medical Research and Development JP21fk0310102Japan Agency for Medical Research and Development JP24fk0310518Japan Agency for Medical Research and Development JP25fk0310543Japan Society for the Promotion of Science 18K15742Japan Society for the Promotion of Science 19K09138Japan Society for the Promotion of Science 24K11147
6 · The paper itself

Abstract

aimIn hepatitis B surface antigen (HBsAg)-negative recipients with antibody to hepatitis B core antigen (anti-HBc)-positive liver grafts, hepatitis B virus (HBV) can be reactivated under post-transplant immunosuppression. We recently reported a median intrahepatic covalently closed circular DNA (cccDNA) level of 238 copies/μg in HBsAg-positive patients. Meanwhile, the potential levels of intrahepatic cccDNA in anti-HBc-positive grafts have never been focused on as a factor for HBV recurrence.

methodsAmong 168 patients who underwent living donor liver transplantation (LDLT) between 2018 and 2022, 4 HBsAg-negative recipients with anti-HBc-positive grafts were consecutively enrolled in this prospective study. Intrahepatic cccDNA levels in donor grafts were measured based on an intraoperative liver biopsy and digital droplet polymerase chain reaction.

resultsIn all four donor grafts, intrahepatic cccDNA levels ranged from 5.2 to 408 copies/μg, and all were negative for the high-sensitivity hepatitis B core-related antigen. Three of four recipients experienced HBV reactivation 14-24 months after LDLT. Two patients developed hepatitis with high HBV DNA and HBsAg levels, escape mutations (G145R ± K141R) with genotype B or C were detected. Entecavir therapy achieved serological and virological clearance within 2-9 months. The fourth patient remained recurrence-free during 36 months of follow-up.

conclusionsEven among patients with resolved HBV infection, there are cases possessing intrahepatic cccDNA levels as high as or even higher than those in HBsAg-positive patients. To resolve this critical pitfall in immunosuppressed patients, the development of serum markers that precisely reflect intrahepatic cccDNA levels will be essential for improving HBV prophylaxis strategies.

Indexed as

DNA, CircularDNA, ViralHepatitis BHepatitis B AntibodiesLiverAdultAllograftsAntiviral AgentsGraft RejectionGuanineHepatitis B Core AntigensHepatitis B Surface AntigensHepatitis B virusHumansImmunosuppressive AgentsLiver TransplantationAntiviral AgentsDNA, CircularDNA, ViralentecavirGuanineHepatitis B AntibodiesHepatitis B Core AntigensHepatitis B Surface AntigensImmunosuppressive Agentsanti‐HBcHBV reactivationintrahepatic cccDNALDLT

Identifiers

PMID41814529
PMCPMC13058777

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.