Hepatitis E epidemics are mainly seen in some developing countries in Asia and Africa, with high susceptibility of pregnant women and easy development of severe hepatitis, and increased morbidity and mortality of pregnant women and perinatal infants. With the improvement of socioeconomic and health standards, hepatitis E outbreaks are rare and mainly disseminated. In this study, we retrospectively analyzed the pregnancy outcomes of 57 patients with hepatitis E infection during pregnancy, which are reported below. Subjects and methods I. General data Fifty-seven pregnant women with abnormal liver function who were hospitalized in the Department of Obstetrics and Gynecology of Shanghai Public Health Clinical Center from January 2006 to December 2010 were diagnosed with HEV infection, and the diagnosis met the diagnostic criteria of the viral hepatitis prevention and control program developed at the 10th National Conference on Viral Hepatitis and Liver Diseases (Xi’an) in 2000. The maternal age ranged from 18 to 39 years, with a median age of 24.8 years, including 38 cases of primigravida, 19 cases of menstrua, 5 cases of early pregnancy, 25 cases of mid-term pregnancy, and 27 cases of late pregnancy. There were 21 cases of Shanghai household registration and 36 cases of foreign household registration. Detection methods and grouping 1. Detection methods: liver and kidney function, serum glycolic acid (CG), hepatitis virus markers and other imaging examinations such as B-mode ultrasound were performed after maternal admission. HEV serum markers were detected by ELISA and HBV serological markers were detected by Roche chemiluminescence immunoassay. 2. Grouping: According to serological markers, we divided into hepatitis E-only group (simple group) and hepatitis B and E overlap infection group (overlap group). Pregnant women with abnormal liver function accompanied by symptoms such as malaise and loss of appetite or with signs such as hepatomegaly, whose anti-HEV-IgM or anti-HEV-IgM and IgG were positive at the same time, and whose other viral markers were negative, were included in the simple group, 35 cases in total. Pregnant women with pre-existing HBV infection (HBsAg-positive and HBV DNA-positive) and abnormal liver function (mainly elevated serum ALT) along with symptoms such as malaise and loss of appetite or signs such as hepatomegaly, whose anti-HEV-IgM or anti-HEV-IgM and IgG were positive at the same time and other viral markers were negative, were included in the overlapping group, 22 cases in total. Forty-six cases were delivered at the Shanghai Public Health Clinical Center, including 24 cases in the simple group and 22 cases in the overlap group. The clinical manifestations, liver function, coagulation index and maternal and infant complications (premature rupture of membranes, preterm delivery, postpartum hemorrhage, severe hepatitis, maternal death, stillbirth, fetal malformation, fetal distress, neonatal asphyxia, fetal growth restriction) were retrospectively analyzed in both groups. III. Statistical methods The SPSS 15.0 software package was used for statistical processing. The measurement data were described by x±s, t-test was used for comparison between the means of two groups, Wilcoxon rank sum test was used for skewed distribution data; X2 test and Fisher’s exact probability method were used for comparison of the rates of count data. p < 0.05 was considered statistically significant difference. Results I. Clinical manifestations and laboratory test results Among 57 pregnant women with HEV infection during pregnancy, there were 25 cases with different degrees of nausea, vomiting, weakness and yellow urine, including 13 cases in the simple group and 12 cases in the overlapping group, and the difference between the two groups was not statistically significant (X2 =1.662, P=0.197). There was no difference in the liver B-mode ultrasound findings between the two groups of pregnant women. ALT and TBil were higher in the overlap group than in the simple group, but the differences were not statistically significant (P value = 0.062 and 0.446, respectively); whereas CG was significantly higher in the overlap group than in the simple group, and the differences were statistically significant (t = 1.807, P = 0.038). The incidence of severe hepatitis in the simple group was 8.3% (2/24); the incidence of postpartum hemorrhage was 8.3% (2/24); and there were no maternal deaths. The fetal and neonatal outcomes were: 1 case of intrauterine death at 31 weeks of gestation, accounting for 4.2% (1/24); 1 case of midterm induction of labor for fetal malformation, accounting for 4.2% (1/24); among 22 live births, 2 cases of prematurity, accounting for 8.3% (2/24), 3 cases of fetal distress, accounting for 12.5% (3/24), and 2 cases of neonatal asphyxia, accounting for 8.3% (2/24). There were 3 cases of severe hepatitis in the overlapping group, with an incidence of 13.6% (3/22), and 3 cases of postpartum hemorrhage, with an incidence of 13.6% (3/22). The maternal mortality rate was 1.8% (1/22). The pregnant woman had an abnormal condition at 34 weeks of gestation with virological indicators suggesting overlapping infections, and the pregnancy was terminated by cesarean section after 48 h of aggressive liver protection and supportive treatment. The fetal and neonatal outcomes were: preterm birth in 4 cases (18.2% (4/22), fetal growth restriction in 3 cases (13.6/0 (3/22), fetal distress in 9 cases (40.9% (9/22), and neonatal asphyxia in 7 cases (31.8% (7/22). There was no statistically significant difference in the incidence of severe hepatitis and maternal morbidity and mortality rate between the two groups (all P > 0.05). In contrast, the incidence of fetal distress, neonatal asphyxia and fetal growth restriction in the overlapping group was significantly higher than that in the simple group, and the difference was statistically significant (all P < 0.05). Table 1 Comparison of liver function and coagulation indexes between the simple and overlapping groups (x±s) Note: Simple group refers to simple hepatitis E virus infection; overlapping group refers to overlapping hepatitis B and E virus infection. a ALT is alanine transaminase; TBil is total bilirubin; CG is glycopyrrolate; PT is prothrombin time. a Wilcoxon rank sum test was used Table 2 Comparison of pregnancy outcome between the simple and overlapping groups Comparison of maternal pregnancy outcomes (cases) Note: Simple group refers to hepatitis E virus infection alone; overlapping group refers to hepatitis B and E virus overlapping infection. The epidemiology and clinical manifestations of hepatitis E are basically the same as those of hepatitis A. However, the degree of jaundice is more severe, the bilious type occurs more often, and the duration of the disease is longer, sometimes more than 6 months, and generally does not turn chronic. The death rate is higher than that of hepatitis A. Due to changes in the immune system and hormone levels during pregnancy, differences in HEV genotypes and environmental factors, pregnant women infected with hepatitis E are prone to acute liver injury, severe disease and high mortality rates. In contrast, studies in Egypt and northern India reported a 3.4% or even zero mortality rate in pregnant women with combined hepatitis E infection, and all of them had normal deliveries. This report is completely different from the 30% to 100% mortality rates reported in other hepatitis E endemic areas, probably because of the differences in the degree of liver damage in infected pregnant women due to different HEV genotypes. Most of the HEV infections in India are type I. The mortality rate of 1.8% in this group is much lower than that of 13.64% during the hepatitis E epidemic in Xinjiang, China, which may be due to the different virulence of different genotypes of HEV, thus causing different damage to the liver of pregnant women. In addition, we do not exclude the possibility of selection bias due to the small sample size of this group. Overlapping HBV and HEV infections are more severe and prolonged than single-HEV infections and are more likely to lead to liver failure, and may increase the incidence of maternal and infant complications. The results of this study showed that the CG level was significantly higher in the overlapping group than in the simple group, indicating that the overlapping group was more prone to cholestasis than the simple group. Although there were more cases of severe hepatitis, maternal death and obstetric complications in the overlap group than in the simple group; the ALT level was also higher than in the simple group, but the difference was not statistically significant, indicating that there was no significant increase in liver damage in pregnant women with overlap infection, and there was no significant increase in the incidence of severe hepatitis, maternal death and obstetric complications in the overlap group compared with the simple group. This phenomenon may be related to the early detection and treatment of liver disease in pregnancy by obstetricians, and whether it is related to the difference in HEV genotype and the special internal environment during pregnancy needs further study. However, the effect of overlapping infections on perinatal infants was significantly more severe than that of hepatitis E alone, and the incidence of fetal growth restriction, fetal distress and neonatal asphyxia was significantly higher in the overlapping infections than in the simple group. Opinions are divided on the mode of delivery for patients with hepatic failure due to combined hepatitis E in pregnancy. Most scholars believe that patients with liver failure in late pregnancy should be terminated by timely cesarean delivery after short-term active treatment, which can reduce the maternal liver burden and improve the prognosis. In our data set of 5 pregnant women with acute liver failure (late pregnancy), all pregnancies were terminated by cesarean section, and one of them died on the third day after cesarean section. However, a case-control study of 42 cases in India showed no statistically significant difference between delivery and maternal morbidity and mortality in patients with combined hepatitis E in pregnancy resulting in liver failure, which also raises questions about the treatment modality of termination of pregnancy. The current study reports do not support the idea that delivery of the fetus reduces the rate of maternal morbidity and mortality. However, because this is a small sample of data, most physicians still choose to terminate the pregnancy promptly, and they believe that HEV-infected mothers also cause alterations in the fetal immune system. There is still no consensus on how to treat co-infection with HEV in pregnancy, and whether early termination of pregnancy is possible to reduce maternal morbidity and mortality is open to further debate. HEV infection during pregnancy is mainly associated with miscarriage, preterm delivery, stillbirth, stillbirth and neonatal asphyxia, and a significant increase in the prevalence and morbidity and mortality of perinatal infants; whether this phenomenon is related to intrauterine HEV infection is unclear. There are few studies on mother-to-child transmission of HEV in China. A foreign study of 469 pregnant women with HEV infection showed a 100% vertical transmission rate, and although selection bias may exist, the high transmission rate of HEV suggests the importance of vertical transmission of HEV infection. A small proportion of newborns born to these women were preterm or jaundice-free, and two of them died within 48 h of birth, while the remaining 24 survived and recovered completely.Khuroo et al. reported that neonatal HEV infection was associated with the severity of the mother's disease. The incidence of fetal distress, neonatal asphyxia and fetal growth restriction was significantly higher in the overlapping group than in the simple group in the present data, and whether this phenomenon is related to the vertical transmission of HEV, in addition to the significantly higher maternal serum CG in the overlapping group, needs to be further clarified. In conclusion, the effect of HEV infection during pregnancy on the perinatal infant is more obvious than that of the mother, mainly manifested by fetal and neonatal hypoxia; early detection and early treatment should be achieved for such pregnant women, and HEV genotype testing should be performed at the same time as active treatment of hepatitis to comprehensively assess the condition of pregnant women with HEV, so as to improve maternal and perinatal prognosis.