Maternal hepatitis E virus infection: Immunopathogenesis, genotype-specific severity, and vertical transmission dynamics

doi:10.4254/wjh.122717

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World Journal of Hepatology

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1948-5182

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Hepatol. Sep 27, 2026; 18(9): 122717
Published online Sep 27, 2026. doi: 10.4254/wjh.122717

Maternal hepatitis E virus infection: Immunopathogenesis, genotype-specific severity, and vertical transmission dynamics

Kashmi Sharma, Megha K Pandey, Ashutosh K Singh, Mudra Sikenis, Bhavna Prajapati, Abhirami Jothish, Prudhvi L Bhukya, Ashish K Vyas, Bojana J Simovic Markovic, Irfan F Corovic, Ram K Nema

Kashmi Sharma, Megha K Pandey, Department of Translational Medicine, All India Institute of Medical Sciences (AIIMS), Bhopal 462020, Madhya Pradesh, India

Ashutosh K Singh, School of Biosciences, Engineering and Technology, VIT Bhopal University, Bhopal 466114, Madhya Pradesh, India

Ashutosh K Singh, Bhavna Prajapati, Ram K Nema, Division of Environmental Biotechnology, Genetics and Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal 462030, Madhya Pradesh, India

Mudra Sikenis, Department of Life Science, Sharda School of Bio-science and Technology, Sharda University, Greater Noida, Noida 201310, Uttar Pradesh, India

Abhirami Jothish, Prudhvi L Bhukya, Rodent Experimentation Facility, ICMR-National Institute for Pre-Clinical Research, Genome Valley, Shamirpet, Hyderabad 500101, Telangana, India

Ashish K Vyas, Amrita Research Center Delhi NCR, Amrita Vishwa Vidyapeetham, Faridabad Campus, Faridabad 110070, Haryana, India

Bojana J Simovic Markovic, Irfan F Corovic, Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia

Irfan F Corovic, Department of Internal Medicine, General Hospital Novi Pazar, Novi Pazar 36300, Serbia

Co-first authors: Kashmi Sharma and Megha K Pandey.

Co-corresponding authors: Irfan F Corovic and Ram K Nema.

Author contributions: Sharma K and Pandey MK contributed equally to this work by conceiving the study, performing the experiments, analyzing the data, and drafting the manuscript, as they are co-first authors; Singh AK contributed to study design, data interpretation, and manuscript preparation; Sikenis M, Prajapati B, Jothish A, Bhukya PL, and Vyas AK participated in data acquisition, experimental procedures, and manuscript revision; Simovic Markovic BJ contributed to the interpretation of immunological findings, scientific discussion, and critical revision of the manuscript; Corovic IF and Nema RK contributed equally as senior authors by supervising the study, providing critical intellectual input, interpreting the data, coordinating manuscript revision, and directing the overall scientific development of the study; all authors reviewed, approved, and agreed to be accountable for all aspects of the work and the final version of the manuscript.

AI contribution statement: Portions of this manuscript were edited using AI tools (ChatGPT, OpenAI, version 5.0) solely for language refinement. The authors carefully reviewed and verified all AI-assisted outputs and take full responsibility for the scientific content of the manuscript.

Conflict-of-interest statement: The authors declare no competing financial interests or personal relationships that could have influenced the work reported in this manuscript.

Corresponding author: Irfan F Corovic, MD, Research Fellow, Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, Kragujevac 34000, Serbia. ira.corovic@gmail.com

Received: April 27, 2026
Revised: July 8, 2026
Accepted: July 29, 2026
Published online: September 27, 2026
Processing time: 144 Days and 19.3 Hours

Abstract

Hepatitis E virus (HEV) infection remains a major global health concern, particularly in regions with poor sanitation and limited access to safe water. Although usually self-limiting in immunocompetent individuals, HEV can cause severe maternal and fetal complications during pregnancy. This review summarizes current evidence on the clinical manifestations, immunopathogenesis, genotype-specific disease patterns, and transmission of HEV in pregnancy. Pregnancy-associated immune modulation, hormonal changes, and placental adaptations promote viral replication and impair antiviral responses, particularly in the later stages of gestation. Disease severity varies by genotype, with human-restricted genotypes 1 and 2 causing the most severe pregnancy outcomes, whereas zoonotic genotypes 3 and 4 generally result in milder disease. Despite advances in understanding HEV pathogenesis, important challenges remain in early diagnosis, risk stratification, and the development of safe preventive and therapeutic strategies for pregnant women.

Keywords: Hepatitis E virus; Pregnancy; Immunopathogenesis; Vertical transmission; Genotype

Core Tip: Pregnancy increases the risk of severe hepatitis E virus infection through immune and hormonal adaptations. This review provides an updated overview of hepatitis E virus pathogenesis, genotype-specific disease, and key challenges in clinical management.