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A 5-year Single-Center Experience of Hepatitis E Virus Infection During Pregnancy. Objective: The study was designed to examine the hypothesis whether the course and severity of hepatitis E virus (HEV)-related liver disease is worse during pregnancy. Method: The prospective study included 1088 patients (550 pregnant; 538 nonpregnant) with clinically and biochemically confirmed acute viral hepatitis (AVH) or acute liver failure (ALF) and were subjected to a complete panel of hepatitis serology. Results: In the pregnant cohort, HEV was the cause of infection in 80.36% (442/550) of cases, whereas non-HEV accounted for 19.63 (108/550) of cases. In the ALF pregnant group, the prevalence of HEV was observed in 73.38% (102/139) of cases, whereas other viruses accounted for 26.61% (37/139) of illness. Ninety-eight of 129 (75.96%) cases of HEV-infected pregnant women died, whereas non-HEV infection was responsible for only 31 of 129 (24.04%) cases' death in comparison. Serum viral load in the ALF group was also significantly higher than that in the AVH group in the pregnant (24578.6 ± 12410.3 vs. 6821.9 ± 1832.7, respectively) cohort and nonpregnant cohort (583.6 ± 187.34 vs. 298.68 ± 65.77, respectively). Conclusion: HEV infection has a higher incidence, more severe course, and greater mortality in the pregnant cohort than in the nonpregnant cohort.