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Diagnostics
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Hepatocellular Carcinoma and Hepatitis: Advanced Diagnosis and Management
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Hepatocellular Carcinoma and Hepatitis: Advanced Diagnosis and Management

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: 1 October 2024 | Viewed by 2882

Special Issue Editors

Dr. Soo Ryang Kim

E-Mail Website
Guest Editor
Kobe Asahi Hospital, Kobe, Japan
Interests: hepatocellular carcinoma; hepatitis C virus; liver disease
Dr. Soo Ki Kim

E-Mail Website
Guest Editor
Department of Gastroenterology, Kobe Asahi Hospital, Kobe, Japan
Interests: hepatitis B virus; NASH

Special Issue Information

Dear Colleagues, 

Although the universal hepatitis B virus (HBV) vaccination program has been successfully implemented for almost three decades in many countries, most HBV-related hepatocellular carcinomas (HCCs) occur in unvaccinated middle-aged and elderly adults. It has been simulated that treating 80% of eligible people could reduce HBV-related deaths by 65% in a short time. However, only 2.2% of CHB patients receive antiviral therapies globally. HBV markers related to HCC occurrence and prevention are as follows. HCC risk is highest with a baseline HBV DNA 6–7 log copies/mL and lowest with a baseline HBV DNA level > 8 log copies/mL and ≤ 4 log copies/mL. (not linear but parabolic pattern). The titer of HBV core-related antigen (HBcrAg) reflecting the amount of HBV covalently closed circular DNA (ccc DNA) in the liver is related to HCC occurrence. Sero clearance of HBs antigen (HBsAg) is more crucial than HBV DNA negativity for the prevention of HCC. In terms of secondary prevention of hepatitis B-related HCC with antiviral therapies with nucleos(t)ide analogues (NAs), there are still unsolved discussions including the definition of the immune-tolerant phase, the optimal time to start the antiviral therapies with NAs, limitations of elevated aminotransferase (ALT) level as a criterion for treatment in CHB patients, normalization of ALT with NAs and risk of HCC, and serum HBV levels and the risk of HCC. In addition, the first-line therapies with NAs such as entecavir (ETV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) remains to be clarified. Therefore, we discuss recent findings of HBV markers related to HCC occurrence and prevention, and unsolved discussions and review the secondary current antiviral therapies for the prevention of HBV-related HCC.

Dr. Soo Ryang Kim
Dr. Soo Ki Kim
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • hepatitis B virus
  • hepatocellular carcinoma
  • nucleos(t)ide analogues
  • secondly prevention
  • HBV DNA
  • immune-tolerant phase
  • hepatitis B virus surface antigen
  • hepatitis B virus core-related antigen
  • covalently closed circular DNA

Published Papers (3 papers)

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Research

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12 pages, 1553 KiB  
Article
Risk Factors for Immune Checkpoint Inhibitor-Induced Liver Injury and the Significance of Liver Biopsy
by Miki Kawano, Yoshihiko Yano, Atsushi Yamamoto, Eiichiro Yasutomi, Yuta Inoue, Jun Kitadai, Ryutaro Yoshida, Takanori Matsuura, Yuuki Shiomi, Yoshihide Ueda and Yuzo Kodama
Diagnostics 2024, 14(8), 815; https://doi.org/10.3390/diagnostics14080815 - 14 Apr 2024
Viewed by 422
Abstract
Immune checkpoint inhibitor (ICI)-induced liver injury (LI) is a common adverse event, but the clinical characteristics based on the classification of hepatocellular injury and cholestatic types are not fully evaluated. This study aims to analyze risk factors and histological findings in relation to [...] Read more.
Immune checkpoint inhibitor (ICI)-induced liver injury (LI) is a common adverse event, but the clinical characteristics based on the classification of hepatocellular injury and cholestatic types are not fully evaluated. This study aims to analyze risk factors and histological findings in relation to the classification of ICI-induced LI. In total, 254 ICI-induced LI patients among 1086 treated with ICIs between September 2014 and March 2022 were classified according to the diagnostic criteria for drug-induced LI (DILI), and their risk factors and outcomes were evaluated. Kaplan–Meier analyses showed that overall survival in patients with hepatocellular-injury-type LI was significantly longer than others (p < 0.05). Regarding pre-treatment factors, the lymphocyte count was significantly higher in patients with ICI-induced LI, especially in hepatocellular-injury-type LI. Gamma glutamyl transferase (γGTP) and alkaline phosphatase (ALP) were also significantly lower in patients with ICI-induced LI (p < 0.05). Multivariate analyses revealed that malignant melanoma, high lymphocyte count, and low ALP levels were extracted as factors contributing to hepatocellular-injury-type LI. The histological findings among 37 patients diagnosed as ICI-induced LI via liver biopsy also revealed that the spotty/focal necrosis was significantly frequent in hepatocellular-injury-type LI, whereas ductular reactions were frequently observed in cholestatic-type LI. It is suggested that the histological inflammation pattern in patients with LI is closely correlated with the type of DILI. Full article
(This article belongs to the Special Issue Hepatocellular Carcinoma and Hepatitis: Advanced Diagnosis and Management)
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Review

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14 pages, 301 KiB  
Review
Clinical Significance and Remaining Issues of Anti-HBc Antibody and HBV Core-Related Antigen
by Yoshihiko Yano, Itsuko Sato, Takamitsu Imanishi, Ryutaro Yoshida, Takanori Matsuura, Yoshihide Ueda and Yuzo Kodama
Diagnostics 2024, 14(7), 728; https://doi.org/10.3390/diagnostics14070728 - 29 Mar 2024
Viewed by 680
Abstract
Currently, hepatitis B virus (HBV) core antibody (anti-HBc antibody) and HBV core-related antigen (HBcrAg) are widely used as serum markers for diagnosis based on the HBV core region. This review focused on anti-HBc antibodies and HBcrAg and aimed to summarize the clinical significance [...] Read more.
Currently, hepatitis B virus (HBV) core antibody (anti-HBc antibody) and HBV core-related antigen (HBcrAg) are widely used as serum markers for diagnosis based on the HBV core region. This review focused on anti-HBc antibodies and HBcrAg and aimed to summarize the clinical significance of currently used assay systems and the issues involved. While anti-HBc is very significant for clinical diagnosis, the clinical significance of quantitative assay of anti-HBc antibody has been reevaluated with improvements in diagnostic performance, including its association with clinical stage and prediction of carcinogenesis and reactivation. In addition, concerning the new HBcrAg, a high-sensitivity assay method has recently been established, and its diagnostic significance, including the prediction of reactivation, is being reevaluated. On the other hand, the quantitative level of anti-HBc antibody expressed in different units among assay systems complicates the interpretation of the results. However, it is difficult to standardize assay systems as they vary in advantages, and caution is needed in interpreting the assay results. In conclusion, with the development of highly sensitive HBcrAg and anti-HBc antibody, a rapid and sensitive detection assay system has been developed and used in clinical practice. In the future, it is hoped that a global standard will be created based on the many clinical findings. Full article
(This article belongs to the Special Issue Hepatocellular Carcinoma and Hepatitis: Advanced Diagnosis and Management)
14 pages, 316 KiB  
Review
Hepatocellular Carcinoma and Hepatitis: Advanced Diagnosis and Management with a Focus on the Prevention of Hepatitis B-Related Hepatocellular Carcinoma
by Soo Ryang Kim and Soo Ki Kim
Diagnostics 2023, 13(20), 3212; https://doi.org/10.3390/diagnostics13203212 - 14 Oct 2023
Viewed by 1138
Abstract
Though the world-wide hepatitis B virus (HBV) vaccination program has been well completed for almost thirty years in many nations, almost HBV-related hepatocellular carcinoma (HCC) occurs in unvaccinated middle-aged and elderly adults. Apparently, treating 80% of qualified subjects could decrease HBV-related mortality by [...] Read more.
Though the world-wide hepatitis B virus (HBV) vaccination program has been well completed for almost thirty years in many nations, almost HBV-related hepatocellular carcinoma (HCC) occurs in unvaccinated middle-aged and elderly adults. Apparently, treating 80% of qualified subjects could decrease HBV-related mortality by 65% in a short period. Nevertheless, globally, only 2.2% of CHB patients undergo antiviral therapy. The HBV markers related to HCC occurrence and prevention are as follows: the HCC risk is the highest at a baseline of HBV DNA of 6–7 log copies/mL, and it is the lowest at a baseline of an HBV DNA level of >8 log copies/mL and ≤4 log copies/mL (parabolic, and not linear pattern). The titer of an HBV core-related antigen (HBcrAg) reflecting the amount of HBV covalently closed circular DNA (ccc DNA) in the liver is related to HCC occurrence. The seroclearance of HBs antigen (HBsAg) is more crucial than HBV DNA negativity for the prevention of HCC. In terms of the secondary prevention of hepatitis B-related HCC involving antiviral therapies with nucleos(t)ide analogues (NAs), unsolved issues include the definition of the immune-tolerant phase; the optimal time for starting antiviral therapies with NAs; the limits of increased aminotransferase (ALT) levels as criteria for therapy in CHB patients; the normalization of ALT levels with NAs and the relation to the risk of HCC; and the relation between serum HBV levels and the risk of HCC. Moreover, the first-line therapy with NAs including entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) remains to be clarified. Discussed here, therefore, are the recent findings of HBV markers related to HCC occurrence and prevention, unsolved issues, and the current secondary antiviral therapy for the prevention of HBV-related HCC. Full article
(This article belongs to the Special Issue Hepatocellular Carcinoma and Hepatitis: Advanced Diagnosis and Management)
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