摘要：Objectives. We estimated the population-based incidence of maternal and neonatal mortality associated with hepatitis E virus (HEV) in Bangladesh. Methods. We analyzed verbal autopsy data from 4 population-based studies in Bangladesh to calculate the maternal and neonatal mortality ratios associated with jaundice during pregnancy. We then reviewed the published literature to estimate the proportion of maternal deaths associated with liver disease during pregnancy that were the result of HEV in hospitals. Results. We found that 19% to 25% of all maternal deaths and 7% to 13% of all neonatal deaths in Bangladesh were associated with jaundice in pregnant women. In the published literature, 58% of deaths in pregnant women with acute liver disease in hospitals were associated with HEV. Conclusions. Jaundice is frequently associated with maternal and neonatal deaths in Bangladesh, and the published literature suggests that HEV may cause many of these deaths. HEV is preventable, and studies to estimate the burden of HEV in endemic countries are urgently needed. Hepatitis E virus (HEV) infection is endemic in Asia and many parts of Africa, where it is a leading cause of sporadic and epidemic acute hepatitis. 1–3 HEV is primarily transmitted through the fecal–oral route, and outbreaks in endemic areas are typically associated with contaminated drinking water sources. 4–13 Clinically, it is indistinguishable from other causes of acute viral hepatitis, and jaundice, the yellowing of the eyes and skin, is the most common clinical feature. 14 Jaundice is caused by a buildup of bilirubin, a product of dying red blood cells, in the blood. The healthy liver removes bilirubin from the blood, but when the liver’s ability to process bilirubin is impaired, the buildup occurs. Additional clinical signs and symptoms include anorexia, malaise, fever, dark urine, vomiting, and stomach pain. 14 Adults are more likely to have HEV disease and antibodies to HEV than are children in endemic areas, which is unexpected given the young ages at which most people are exposed to other enteric pathogens in low-income countries. 15 In general, fewer than 1% of patients with clinical HEV die, but case fatality ratios among pregnant women have been reported to be as high as 6% to 20%. 12,14,16–18 A high case fatality rate among pregnant women is a characteristic feature of HEV that has not been observed for other etiologies of acute viral hepatitis. 19 Pregnant women whose deaths are associated with HEV typically die of hemorrhage or hepatic neuropathy. 20,21 The few studies that investigated vertical transmission of HEV noted that neonates born to mothers with HEV infections were frequently infected and often died from complications such as prematurity, liver failure, hypothermia, or hypoglycemia. 21–25 Hepatitis is not considered to be an important cause of maternal or neonatal mortality globally, 26–28 but some data suggest that acute hepatitis might significantly contribute to maternal mortality in HEV endemic countries. A retrospective, community-based study of maternal mortality from southern India reported that 11% of maternal deaths were attributable to infectious hepatitis, resulting in a maternal mortality ratio of 8 per 1000 live births. 29 Another record review of maternal mortality from Ethiopia concluded that 15% of maternal deaths were the result of infectious hepatitis. 30 An autopsy study from India found that the most common cause of maternal deaths at 1 large hospital was acute viral hepatitis, which accounted for 42% of all maternal deaths. 31 Notably, none of these studies provided evidence about the etiology of these hepatitis illnesses, so it is not known if they were caused by HEV. However, given that HEV is a particularly fatal cause of acute hepatitis among pregnant women, 19 the possibility that HEV could meaningfully contribute to maternal mortality in these countries should be considered. However, to our knowledge, no studies have attempted to quantify the burden of HEV-associated maternal and neonatal mortality. In low-income countries in Asia and Africa where HEV is commonly found, 1–3 population-based estimates of mortality usually come from verbal autopsy studies that use structured questionnaires to interview relatives of the deceased about signs and symptoms of illness before death, and then use coding algorithms to determine cause of death based on the interview data. 32 The verbal autopsy questionnaires include questions about new onset of jaundice before death in pregnant women, or new onset of jaundice in the mother as a complication of pregnancy for neonatal deaths. Thus, data from verbal autopsy studies can be used to calculate population-based estimates of maternal and neonatal mortality associated with jaundice. However, the nature of these data precludes conclusions about deaths from specific infectious etiologies, such as HEV. Hospital-based studies can provide important information about etiologic causes of maternal and neonatal deaths associated with jaundice that occur in hospital settings of HEV endemic countries. We investigated the possible contribution of HEV to maternal and neonatal mortality by analyzing data from 4 population-based verbal autopsy studies in Bangladesh and comparing these data with the published literature from hospital-based studies of the etiologic causes of jaundice-associated deaths during pregnancy.
