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Analyses of Clinical and Biological Data for French and Belgian Immunocompetent Patients Infected With Hepatitis E
Florence Micas1, Vanessa Suin2, Jean-Marie Péron3
1Virology Laboratory, National Reference Centre of Hepatitis E Viruses, Federal Institute of Biology, University Hospital Center, Toulouse, France.
Insights
Hepatitis E virus (HEV) genotype 4 infections in immunocompetent patients are associated with higher liver enzyme levels and a greater risk of mortality compared to genotype 3. Further research is needed to understand genotype-specific HEV pathophysiology.
Area of Science:
- Hepatology
- Virology
- Infectious Diseases
Background:
- Hepatitis E virus (HEV) genotypes 3 and 4 are significant causes of acute hepatitis in industrialized nations.
- Genotype 3 is prevalent in Europe and the Americas, while genotype 4 is common in Asia.
- Previous studies suggest HEV genotype 4 may be more virulent than genotype 3.
Purpose of the Study:
- To compare the clinical and biological characteristics of HEV genotype 4 infections with HEV genotype 3 infections in immunocompetent patients.
- To investigate potential differences in disease severity and outcomes between HEV genotypes 3 and 4.
Main Methods:
- A case-control study analyzing clinical and biological data from 27 immunocompetent patients with HEV genotype 4 infection.
- Patients with HEV genotype 4 were matched for age and gender with two patients infected with HEV genotype 3.
- Bivariate and stepwise regression analyses were used to compare outcomes and identify significant predictors.
Main Results:
- HEV genotype 4-infected patients exhibited significantly higher alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin levels at diagnosis compared to HEV genotype 3 patients.
- Patients with HEV genotype 3 were more likely to report dark urine and asthenia.
- Two deaths due to multi-organ failure occurred in the HEV genotype 4 group, whereas no deaths were observed in the HEV genotype 3 group (p = 0.035).
Conclusions:
- HEV genotype 4 infection is associated with more severe liver enzyme elevation and potentially higher mortality risk than HEV genotype 3 infection in immunocompetent individuals.
- The findings suggest a greater virulence of HEV genotype 4.
- Further immunological and virological studies are warranted to elucidate the mechanisms underlying genotype-specific HEV pathophysiology.
Abstract:
Hepatitis E virus (HEV) genotypes 3 and 4 are the major causes of acute hepatitis in industrialized countries. Genotype 3 is mainly found in Europe and America, while genotype 4 is predominant in Asia. Several Japanese studies have suggested that genotype 4 is more virulent than genotype 3. We investigated this aspect by analyzing the clinical and biological data for 27 French and Belgian immunocompetent patients infected with HEV genotype 4. Their infections were probably acquired locally, since none of these patients reported traveling outside France or Belgium during the 2-8 weeks before symptoms onset. Each patient was matched for age (±5 years) and gender with two patients infected with HEV genotype 3. Bivariate analysis indicated that the HEV genotype 4-infected patients had significantly higher alanine aminotransferase (ALT) (2067 IU/L) and aspartate aminotransferase (AST) (1581 IU/L) activities and total bilirubin concentrations (92.4 μmol/L) than did those infected with HEV genotype 3 (1566 IU/L, p = 0.016; 657 IU/L, p = 0.003 and 47 μmol/L, p = 0.046) at diagnosis. In contrast, more patients infected with HEV genotype 3 reported dark urine (71% vs. 39%, p = 0.02) and experienced asthenia (89% vs. 58%, p < 0.01) than did those infected with HEV genotype 4. Two HEV genotype 4-infected patients died of multi-organ failure, while none of the genotype 3-infected patients died (p = 0.035). Finally, stepwise regression analysis retained only a greater increase in ALT (odds-ratio: 1.0005, 95% confidence interval: 1.00012-1.00084) and less frequent fever (odds-ratio = 0.1244; 95% confidence interval: 0.01887-0.82020) for patients infected with HEV genotype 4. We conclude that HEV-4 infections are likely to be associated with higher ALT activity than HEV-3 infections. Additional immunological and virological studies are required to confirm these findings and better understand the influence, if any, of genotype on HEV pathophysiology.
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