The Unmet Needs of Hepatitis E Virus Diagnosis in Suspected Drug-Induced Liver Injury in Limited Resource Setting

Mohamed A El-Mokhtar; Haidi Karam-Allah Ramadan; Marwa M Thabet; Alaa S Abd-Elkader; Magdy Fouad; Mohammad M Sallam; Elsayed A Elgohary; Amer Ali Abd El-Hafeez; Mona Embarek Mohamed; Ibrahim M Sayed

doi:10.3389/fmicb.2021.737486

The Unmet Needs of Hepatitis E Virus Diagnosis in Suspected Drug-Induced Liver Injury in Limited Resource Setting

Front Microbiol. 2021 Oct 8:12:737486. doi: 10.3389/fmicb.2021.737486. eCollection 2021.

Authors

Affiliations

¹ Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Asyut, Egypt.
² Microbiology and Immunology Department, Faculty of Pharmacy, Sphinx University, Asyut, Egypt.
³ Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Assiut University, Asyut, Egypt.
⁴ Department of Clinical pathology, Faculty of Medicine, Assiut University, Asyut, Egypt.
⁵ Hepato-Gastroenterology Unit, Tropical Medicine Department, Faculty of Medicine, El-Minia University, Minya, Egypt.
⁶ Department of Internal Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
⁷ Pharmacology and Experimental Oncology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
⁸ Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, CA, United States.

Abstract

Background: Currently, there are no specific biomarkers for drug-induced liver injury (DILI), and the diagnosis of DILI is based mainly on the exclusion of other causes of liver dysfunction and the recognition of potential causative drugs. Hepatitis E virus (HEV) diagnosis is not routinely enrolled in many countries, and HEV infection could be misdiagnosed as DILI. Methodology: We retrospectively analyzed plasma samples (n = 80) collected from suspected DILI for HEV markers such as anti-HEV IgM, anti-HEV IgG, and HEV RNA. Anti-HEV antibodies were assessed using commercial ELISA kits. HEV RNA was tested by RT-qPCR targeting HEV ORF2/3, the receiver operating characteristic (ROC) curve was plotted, and a putative threshold for liver function parameters was determined. Results: Out of 80 samples, 12 samples were positive for anti-HEV IgM and anti-HEV IgG, and HEV RNA was detected in seven samples. The median viral load was 3.46 × 10³ IU/ml, and the isolated viruses belonged to HEV genotype 1. The level of liver enzymes such as alanine transaminase (ALT) and aspartate transaminase (AST), but not alkaline phosphatase (ALP), was significantly higher in HEV confirmed cases than in non-HEV confirmed cases. We identified a plasma ALT level of at least 415.5 U/L and AST level of at least 332 U/L; ALT/ALP ratio of at least 5.08 could be used as a guide for the patients diagnosed as DILI to be tested for HEV infection. The previous liver function parameters showed high sensitivity and good specificity. Conclusion: Hepatitis E virus was detected in suspected DILI cases. The diagnosis of DILI is not secure until HEV testing is done. Liver function parameters can be used as a guide for HEV testing in suspected DILI cases in countries with limited resources.

Keywords: DILI; HEV; acute hepatitis; limited resource countries; liver function test; screening.