Iranian Journal of Pathology

Circulating HBcrAg, miRNA-122, and M2BPGi as Predictive Biomarkers for Hepatocellular Carcinoma in Chronic Hepatitis B Patients: A Case-Control Study

Articles in Press

Document Type : Original Research

Authors

Amgad Ahmed Ezzat Othman 1
Mohamed S Hemeda 2
Khaled Mohamed Hassanein Mohamed 3
Mohammed Saad Ahmed 1
Ayman S Yassin 1
Mohamed Nabil Mohamed 1
Abd Elmoaty Arafat Abd Elmoaty 4
Mahmoud M. Khafagi 4
Mohammed Mostafa Mohammed Abdo Mostafa Mohammed Abdo 1
Mohamed Abdel Basit Ibrahim Mohamed 1

1 Department of Medical Microbiology and Immunology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt

2 Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Port Said University, Port Said, Egypt

3 Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt

4 Hepatology and Infectious Diseases Department, Faculty of Medicine, Al-Azhar University, Assiut, Egypt

10.30699/ijp.2026.2075531.3567
Abstract
Background & Objective: Hepatitis B Virus (HBV) infection has highly negative consequences for the global population, with chronic hepatitis B (CHB) infection and the resulting hepatocellular carcinoma (HCC) representing one of the most concerning long-term outcomes. This study focuses on the use of several biomarkers (miRNA-122, HBcrAg, and M2BPGi) in liquid biopsies to evaluate their efficacy in detecting early-stage HCC and assessing risk in patients with CHB.
Methods: This study included 90 participants. Of these participants, 30 had chronic hepatitis B (CHB), 30 had hepatocellular carcinoma with HBV (HCC), and 30 were healthy controls. Serum miRNA-122 was quantified with real-time PCR, and HBcrAg and M2BPGi were measured using ELISA.
Results: MiRNA-122 had an AUC of 0.801 and a sensitivity of 85.2%, indicating the highest diagnostic performance among the studies evaluated. M2BPGi demonstrated strong performance, with an AUC of 0.84. By contrast, HBcrAg had a very weak discriminative value. These previously stated biomarkers can improve the peripheral non-invasive screening.
Conclusion: In this initial cohort study, circulating miRNA-122 and M2BPGi demonstrate an unsuspected capacity to predict HCC differentiation in CHB patients. However, these are preliminary and have yet to be tested for robustness across multicenter studies with appropriately estimated sample sizes.

Keywords

miRNA-122
HBcrAg
M2BPGi
Hepatocellular carcinoma
Chronic hepatitis B
Forensic biomarkers
Toxicological relevance

Subjects

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Iranian Journal of Pathology

Articles in Press, Accepted Manuscript
Available Online from 20 February 2026

  • Receive Date 22 October 2025
  • Revise Date 28 December 2025
  • Accept Date 20 January 2026

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