Dou J, Zhao XY, Wang ZG, Ning ZH, Wang XZ, Guo F. Hepatitis B virus and hepatitis D virus co-infection complicated by autoimmune hepatitis: Two case reports. World J Clin Cases 2025; 13(26): 104421 [DOI: 10.12998/wjcc.v13.i26.104421]
Corresponding Author of This Article
Feng Guo, Professor, Department of Hepatology, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, No. 116 Huanghe Road, Shayibak District, Urumqi 830000, Xinjiang Uygur Autonomous Region, China. gf_sj@163.com
Research Domain of This Article
Infectious Diseases
Article-Type of This Article
Case Report
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Jing Dou, Zhuan-Guo Wang, Zhong-Hui Ning, Xiao-Zhong Wang, Feng Guo, Department of Hepatology, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi 830000, Xinjiang Uygur Autonomous Region, China
Xin-Yan Zhao, Department of Liver Transplantation Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
Author contributions: Dou J and Guo F revised the paper; Dou J contributed to writing and statistical analysis; Zhao XY contributed to issue the pathological reports of the liver; Wang ZG and Ning ZH contributed to data analysis and performing experiments (follow up patients); Wang XZ contributed to resources and supervision; Guo F contributed to study design and conception.
Supported by Xinjiang “Tianshan Talents” Medical and Health High-Level Talent Training Program-Young and Middle-Aged Backbone Medical Talents.
Informed consent statement: Informed consent was obtained from both patients.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Feng Guo, Professor, Department of Hepatology, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, No. 116 Huanghe Road, Shayibak District, Urumqi 830000, Xinjiang Uygur Autonomous Region, China. gf_sj@163.com
Received: March 19, 2025 Revised: April 2, 2025 Accepted: May 28, 2025 Published online: September 16, 2025 Processing time: 215 Days and 20.8 Hours
Abstract
BACKGROUND
Hepatitis D virus-hepatitis B virus (HDV-HBV) co-infection accelerates liver disease progression and increases the risk of hepatocellular carcinoma, but the immunopathogenic mechanism of its combination with autoimmune hepatitis (AIH) has not been clarified. This study reveals for the first time that HDV may induce AIH through abnormalities in immunoregulation in two specific cases. This is the first report of HDV-HBV co-infected patients who did not receive interferon therapy and achieved serological conversion and histological remission by combining antiviral (entecavir) with immunosuppression (prednisone + azathioprine) therapy, providing new evidence of the mechanism of this complex disease.
CASE SUMMARY
A 40-year-old female developed malaise and jaundice with an alanine aminotransferase/aspartate aminotransferase > 20 upper limit of normal (ULN), total bilirubin: 97.20 μmol/L, immunoglobulin G (IgG) 47.1 g/L (> 3 × ULN), HDV RNA 1.6 × 107 copies/mL and liver biopsy showed G3S4. Tenofovir alafenamide combined with prednisone and azathioprine was administered, and three months later the Child-Turcotte-Pugh class C was reduced to class B and IgG decreased to 13.62 g/L. Another 58-year-old male complained of pain in the liver area, anti-nuclear antibody was 1:320, IgG 22.6 g/L (> 1.3 × ULN), and liver biopsy showed G2S3. Entecavir was administered in combination with prednisone and azathioprine, and after 3 months, liver function returned to normal, and IgG reduced to 14.22 g/L.
CONCLUSION
Patients with HDV-HBV co-infection combined with AIH can achieve clinical remission following combination therapy, and the study of immunomodulatory mechanisms should be emphasized.
Core Tip: This study reports, for the first time, two patients with hepatitis D virus (HDV)-hepatitis B virus co-infection combined with autoimmune hepatitis (AIH) who were not treated with interferon and achieved serological conversion and histological remission with antiviral drugs (entecavir/tenofovir alafenamide) in combination with immunosuppression (prednisone + azathioprine). Patients with severe HDV-related liver disease should be routinely screened for autoantibodies to avoid exacerbation by interferon therapy. The combination therapy was effective in controlling HDV-hepatitis B virus co-infection associated AIH, suggesting that aberrant immunoregulation may be an important mechanism of HDV-induced AIH, providing new evidence for elucidating the pathogenesis of this complex disease, and emphasizing the necessity of immune mechanism research.
