Management of viral hepatitis A,C, D and E in pregnancy

Viral hepatitis can cause significant maternal and neonatal morbidity and mortality. Hepatitis A and E mainly present as acute hepatitis during pregnancy, while hepatitis C and D are usually found as chronic infection in pregnant women. Hepatitis A remains self-limiting during pregnancy while hepatitis E has a higher prevalence and manifests with a rigorous course in pregnant women. Screening of hepatitis C during pregnancy and its subsequent management during pregnancy are still a debatable topic. New treatments of hepatitis C and E require further evaluation for use in pregnancy. This review summarizes the prevalence, clinical manifestations, maternal, foetal and neonatal effects, and the management of hepatitis A, C, D and E viral infection during pregnancy.     

Viral infections in pregnancy

Viral infections are a common complication of pregnancy and in some cases, can have profound effects for the unborn fetus. The human herpesvirus family is composed of large, enveloped DNA viruses that have close structural similarity. The family includes the herpes simplex viruses types 1 and 2, varicella zoster virus, Epstein Barr virus, cytomegalovirus (CMV), and human herpes viruses types 6, 7 and 8. These viruses all share the ability to establish latency and reactivate at a later time. Structural fetal abnormalities can result from intrauterine infection and transmission of the infection during the pregnancy or at the time of delivery can result in important neonatal disease. Human parvovirus B19 is a DNA virus with strong tropism for erythroid precursors and infection during pregnancy can result in fetal hydrops and stillbirth. The causative agents of hepatitis are hepatotropic viruses termed hepatitis A, B, C, D (deltavirus) and E. All except hepatitis B virus are RNA viruses. Vertical transmission of maternal infection with hepatitis B and C can result in significant long term sequelae.     

Viral hepatitis during pregnancy

Viral hepatitis is one of the most common liver diseases appearing during pregnancy. Prevention against hepatotropic viruses is restricted due to lack of vaccines being effective in induction of efficient immunization in the majority of these microorganisms. In general, there is no possibility of active immunization against hepatotropic viruses except type A and B viral hepatitis. An issue of viral hepatitis in pregnancy as an aspect of potential risk factor connected with infection of pregnant women and a fetus has been described in this paper. Furthermore, the most important topics in the field of the epidemiology, prophylaxis and possible treatment options of viral hepatitis A, B, C, D, E and G have been discussed. The newest reports of pregnant women lamivudine therapy as a preventive treatment against vertical transmission during delivery have been reviewed. Rarly diagnosed viral hepatitis caused by herpes simplex virus, cytomegalovirus, Epstein-Barr virus and adenoviruses have been characterized as well.     

妊娠合并重症肝炎29例临床分析

目的探讨妊娠合并重症肝炎的发病情况与有关围产期正确处理方式，减少对母儿的威胁。方法对我院近8年来29例妊娠合并重症肝炎的病例进行回顾性分析，通过分析其临床表现、病毒标志物、血生化、B超、病理观察、临床处理与妊娠结局，总结对该病的诊治经验和教训。结果急性重症肝炎7例（乙型3例、乙丙重叠感染1例、乙戊重叠感染2例、戊型1例），亚急性重症肝炎11例（乙型7例、戊型1例、病毒阴性3例），慢性重症肝炎11例（乙型10例、病毒阴性1例）。孕产妇预后：治愈2例、好转13例、未愈自动出院5例、死亡9例，死亡率为31．0％。死胎1例，死产2例，新生儿死亡4例，新生儿存活率占69．2％，围产儿死亡率为43．8％。结论妊娠合并重症肝炎严重危及母婴生命安全，是产科严重的合并症之一，定期产前教育和检查及早发现和处理是关键。     

Hepatitis B – chronic carrier status and pregnancy outcomes: An obstetric perspective

Antenatal screening for hepatitis B surface antigen (HBsAg) only identifies women with hepatitis B virus (HBV) infection for neonatal immunoprophylaxis. It does not reflect the phase of chronic infection, viral genotype and activity, hepatic inflammation, or other co-existing liver disorders. Coinfection with other viruses and micro-organisms may also be present. These factors in various combinations can impact pregnancy outcomes, and they are probably responsible for the conflicting literature on this issue. Pregnancy complications may interact with maternal HBV infection and hepatitis flares, leading to serious and lethal complications. Hepatitis flares are common especially postpartum, and they are unpredictable and unpreventable with antiviral treatment. Evidence on the association between HBsAg seropositivity with gestational diabetes mellitus, preterm birth, increased foetal growth, and reduced pregnancy hypertensive disorders is stronger than other adverse pregnancy outcomes. Baseline assessment of liver function, and viral markers and activity, can delineate the truly high-risk pregnancies for close monitoring.     

人巨细胞病毒在妊娠期筛查中的意义

人巨细胞病毒是一种在人体各种器官和组织中广泛存在的病毒。先天性的巨细胞病毒感染是新生儿视力障碍、先天性感音神经性耳聋、病毒性肝炎、病毒性肺炎等疾病的常见原因。妊娠期针对高危孕妇和胎儿进行筛查是临床干预的重要环节。     

New emerging blood-borne hepatitis viral pathogens and the feasibility of passing thorough the placenta: an appraisal

In countries with a high prevalence of blood-borne pathogen infections, transmission to infants commonly occurs from an infected mother during pregnancy. Maternal diseases caused by bacteria, viruses and parasites may sometimes be transmitted vertically. For many pathogens, several questions remain unanswered about the pathogenesis of vertical transmission, the relative risk associated with each mode of transmission, the rate of transmission from mother to child, and the factors that might contribute to the efficiency of transmission. There is also a need to quantify the contribution made by intrauterine versus intrapartum events. Here, the feasibility of some new emerging blood-borne hepatitis viral pathogens (hepatitis G virus, hepatitis SEN virus and hepatitis TT virus) passing through the placenta was analyzed based on a consideration of nonostructure level. Based on the particle size as a single factor, it is hereby proposed that the transmission of the studied viruses via the placenta is difficult. Possible infection due to other processes, especially intrapartum infection due to micro-trauma delivery, similar to HIV infection, might be a more important route of vertical transmission.     

Pure red cell aplasia and acute hepatitis during pregnancy

Pure red cell aplasia during pregnancy is rare. We present a case in a 26-year-old pregnant woman, referred to our hospital at 31 weeks' gestation because of severe anemia caused by acute hepatitis. She was treated with repeated blood transfusions and the pure red cell aplasia gradually remitted during the pregnancy. A live infant was delivered by cesarean section at 34 weeks' gestation. Postpartum, the pure red cell aplasia and hemolytic anemia remitted completely. Our case illustrates that pure red cell aplasia may occur late in pregnancy associated with acute viral hepatitis and is reversible during pregnancy without any necessity for steroid therapy.     

Overview of infection causing hepatitis other than non-A to E hepatitis virus during pregnancy

Abnormal liver function tests during pregnancy are common. While hepatic injury during pregnancy mostly has minimal adverse influence on maternal and fetal outcomes, severe maternal and fetal morbidities, and even death, sometimes occur. Here, we review the epidemiology, clinical features, diagnosis, and management of hepatitis during pregnancy caused by the less common pathogens, including Epstein–Barr virus (EBV), cytomegalovirus (CMV), herpes simplex viruses (HSVs), dengue fever, malaria, leptospirosis, Q fever, typhoid fever, and other occasional infections, as well as the implications on breastfeeding of the infants. Hepatitis during pregnancy with fever and systemic clinical presentations, which are not attributable to the common infectious agents, should raise the suspicion of infection with above-mentioned pathogens, and appropriate laboratory tests are required. Early recognition of severe hepatitis or acute liver failure is critical in initiating appropriate and specific therapy, together with systemic supportive care, to reduce maternal and fetal mortality and long-term sequelae.     

Varicella-zoster virus: Prevention through vaccination

Widespread use of varicella vaccine in the United States has drastically changed the epidemiology of the disease. Although chickenpox is no longer a ubiquitous childhood infection, varicella-zoster virus continues to circulate in the community and nonimmune pregnant women remain at risk. Varicella can cause severe infection in pregnant women, often complicated by viral pneumonia. Maternal varicella occurring in the first half of pregnancy can cause the rare but devastating congenital varicella syndrome, whereas infection in the late stages of pregnancy may cause neonatal varicella. The best approach to avoiding the morbidity and mortality associated with chickenpox in pregnancy is to screen and vaccinate susceptible reproductive-age women.     

The chasm between public health and reproductive research: what history tells us about Zika virus

Zika transmission from mother to fetus and its possible sexual transmission have become a media focus in the past months as a major public health concern. While mother-to-fetus transmission, fetal neurologic manifestations or sexual transmission have never been documented for this virus before, other viruses that belong to the same family are very well known to reproductive health workers, clinicians, and researchers. As a member of Flaviviridae family, including hepatitis C and bovine viral diarrhea virus (BVDV), Zika’s pathogenesis may have some parallels with these infections which may pose future questions for public health and research. Vertical transmission of hepatitis C virus from mother to child is known to occur in up to 10 % of pregnancies. BVDV, a member of Pestivirus genus of Flaviviridae family is not known to be transmitted to humans but is known for its vertical transmission in cattle. BVDV infection at different stages of gestation may lead to a spectrum of adverse pregnancy outcomes, including pregnancy loss and neurologic manifestations (including deformations such as hydrocephalus and microcephaly) in the offspring. Similar to hepatitis C, which is a virus of Hepacivirus genus, BVDV is capable of persistent infection, meaning that virus may stay in mother and future generations of calves may be infected as well, which may, in turn, result in persistence of infection in offspring. Would this be a case with Zika virus? Along with mother-to-fetus transmission, sexual transmission is a concerning implication for Zika virus. Would woman become a persistent career or male be able to persistently carry virus with its sperm is yet unknown; yet, there is a concern for the reservoir of infection. Animal models of the disease are urgently needed not only to demonstrate the mother-to-fetus transmission and confirm the fetal neurologic manifestations but also to address the effects of virus on life-long host’s immunity and reproductive health. Along those lines, women desiring pregnancies who are identified to travel, have a partner traveling to, or living in the areas of Zika infections should be encouraged to have a preconception consultation with maternal-fetal medicine.     

Guideline No. 409: Intrauterine Fetal Diagnostic Testing in Women with Chronic Viral Infections

ObjectiveThis revised guideline provides updated information for the care of women with chronic viral infections who require intrauterine fetal diagnostic testing.Target PopulationWomen with chronic viral infections who are pregnant or planning a pregnancy.OptionsNon-invasive screening tests for diagnosis: maternal serum placental analytes with or without nuchal translucency, sonography, maternal serum cell-free placental DNA; and intrauterine fetal diagnostic testing: amniocentesis, chorionic villus sampling, cordocentesis.OutcomesThe recommendations in this guideline have the potential to decrease or eliminate morbidity and mortality in women with chronic viral infections and their infants, which is associated with significant health and economic outcomes.EvidencePublished literature was retrieved through searches of PubMed, guidelines of national societies (Society of Obstetricians and Gynaecologists of Canada, American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine, other international societies), and the Cochrane Library using appropriate controlled vocabulary (amniocentesis, chorionic villus sampling, cordocentesis, procedure pregnancy loss risk, viral vertical transmission, fetal and neonatal infection) and keywords (maternal infection or exposure, hepatitis B, hepatitis C, human immunodeficiency virus). Results were restricted to systematic reviews, randomized controlled trials or controlled clinical trials (if available), and observational case-control studies or case series from 2012 to 2019 published in English or French. Studies from 1966 to 2002 were previously reviewed in the SOGC guideline No. 123: Amniocentesis and Women with Hepatitis B, Hepatitis C, or Human Immunodeficiency Virus, and those from 2002 to 2012 were previously reviewed in the SOGC guideline No. 309: Prenatal Invasive Procedures in Women With Hepatitis B, Hepatitis C, and/or Human Immunodeficiency Virus Infections. Updated literature searches were completed regularly through August 2019 and were incorporated into this guideline.Validation MethodsThe authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations).Intended AudienceThe intended users are maternity care providers and women with chronic viral infections. This guideline provides information to educate and counsel these women, and to offer them reproductive options.RECOMMENDATIONS (GRADE ratings in parentheses)

• 1For women with a chronic infection with hepatitis B, hepatitis C, and/or human immunodeficiency virus (HIV), the use of non-invasive methods of fetal aneuploidy risk assessment is recommended, using screening tests with high sensitivity and low false-positive rates (maternal serum placental analytes with or without nuchal translucency, detailed sonography [dating crown-rump length, first- and second-trimester anatomic] and maternal serum cell-free placental DNA as first- or second-tier screening test) (strong, moderate).
• 2When counselling pregnant women with a chronic infection that can pose a risk of perinatal morbidity regarding intrauterine fetal diagnostic genetic and/or infectious testing:
  • •The pregnancy loss rate (spontaneous loss rate and rate due to the procedure) discussed should be based on the gestational age at the time of the procedure (strong, high).
  • •The first trimester (when chorionic villus sampling is performed) has an estimated spontaneous pregnancy loss rate of 1.40% (based on a population cohort of maternal age >36 years with normal first-trimester sonographic screening); the second trimester (when amniocentesis is performed) has an estimated spontaneous pregnancy loss rate of 0.65% (based on a population cohort of maternal age >36 years with normal second-trimester sonographic screening) (strong, high).
  • •The estimated risk of pregnancy loss due to amniocentesis is 0.35% to 1.00%, based on systematic reviews or meta-analyses, cohort studies with control groups, and randomized controlled trials; the risk varies depending on provider expertise (strong, high).
• 3When performing sonography-guided amniocentesis for women with a chronic hepatitis B, hepatitis C, and/or HIV infection, every effort should be made to avoid the amniocentesis needle going through the placenta or within 1 to 2 cm of the implantation placental edge (strong, moderate).

• Hepatitis B

• 4Hepatitis B virus DNA load should be evaluated in women with positive hepatitis B surface antigen status who require intrauterine fetal diagnostic testing. A viral DNA load >200 000 IU/mL or >10⁶ copies/mL and positive hepatitis B e antigen status increase the risk of vertical transmission (strong, moderate).
• 5In women with chronic hepatitis B infection and a significant viral load (>200 000 IU/mL or >10⁶ copies/mL), maternal antiviral therapy should be considered in order to decrease the vertical transmission risk. The first-line antenatal antiretroviral agent tenofovir is recommended (strong, moderate).

• Hepatitis C

• 6In women with chronic hepatitis C infection, amniocentesis is recommended over chorionic villus sampling due to the limited data available on chorionic villus sampling (conditional, low).
• 7Amniocentesis in women with a chronic hepatitis C infection does not appear to significantly increase the risk of vertical transmission of the virus; however, there is limited published cohort data, and this information should be shared with the patient during the informed consent process (conditional, low).

• HIV

• 8Pregnant women with HIV have reported pregnancy loss rates after amniocentesis of 2.6% to 22% (although only small cohorts have been reported) and vertical transmission rates of 0% to 2.3%. Data evaluating the clinical use of amniocentesis among women with HIV is increasing but still limited, and this information should be shared with women during the informed consent process (conditional, low).
• 9Amniocentesis in women with HIV who are treated with combination antiretroviral therapy appears to pose no increased risk of vertical transmission of HIV, especially if the antiviral therapy reduces the maternal viral load to undetectable levels (strong, high).

     

Acute liver failure in pregnancy. A case report

BACKGROUND: Liver disease in pregnancy can be grossly divided into those disorders coincidentally occurring during the pregnant state and hepatic diseases limited to pregnancy. Numerous infectious agents can result in acute hepatitis and include not only the hepatitis viruses--A, B, C and E--but herpesvirus and cytomegalovirus as well. Coxsackie B viruses can cause several clinical presentations, ranging from asymptomatic to mild febrile illness to myocarditis and meningitis. Rarely has coxsackievirus infection been associated with fulminant hepatic failure. CASE: A Coxsackie B virus infection resulted in acute liver failure in a gravid woman. The patient was managed expectantly, with resolution of the liver disease and delivery five weeks after discharge. CONCLUSION: The onset of hepatic disease is insidious, with only vague symptoms or minor complaints often heralding the progression to liver failure. A careful history, physical examination and appropriate diagnostic tests can help determine the etiology of hepatic disease and help decide whether expectant management of the gravid patient or immediate delivery is appropriate.     

Hepatitis B – Vertical transmission and the prevention of mother-to-child transmission

Hepatitis B virus (HBV) infection is the commonest cause of chronic hepatitis, with an estimated global prevalence of 3.5%, and which leads to significant morbidity and mortality. Mother-to-child transmission (MTCT) during pregnancy is the leading form of transmission in endemic populations, and its interruption is thus crucial as the initial step in the elimination of HBV infection, notwithstanding the availability of potent antiviral medications. The risk of MTCT is dramatically reduced by timely neonatal HBV vaccination and the administration of hepatitis B immunoglobulin after birth in high-risk infants. Maternal HBV DNA quantification during pregnancy allows the assessment of the risk of newborn immunoprophylaxis failure (IF). Maternal antiviral treatment in highly viremic women can reduce the risk of IF. However, the optimal HBV DNA cutoff level for the initiation of antiviral treatment remains to be determined.     

Ausgewählte tropische Infektionskrankheiten in der Schwangerschaft

About 500,000 pregnant women and 4 million babies die during the first 4 weeks of life every year, and in the last 3 months of pregnancy 4 million babies are stillborn; 99% of these deaths occur in developing countries, reflecting the poor standard of medical care and hygiene. The high mortality of pregnant women and newborns is due to malnutrition, bleeding, anemia, hypertension, miscarriage, abortion, obstructed labor, and infections. High-risk infections for pregnant women and their unborn children are Plasmodium falciparum malaria, helminthic infections, hemorrhagic fever viruses, hepatitis E, but also toxoplasmosis, tetanus, puerperal sepsis, and HIV. Pregnant women should be discouraged from traveling to tropical areas and countries with poor standards of hygiene and medical care. When undertaking a journey, pregnant travelers should be vaccinated against tetanus, poliomyelitis, diphtheria, measles, mumps, rubella, and varicella. Depending on the destination prophylaxis or vaccinations for malaria, hepatitis A and B, typhoid fever, yellow fever, meningococci, rabies, and Japanese encephalitis are recommended. If possible, all these vaccines should be administered before the pregnancy.     

Lebererkrankungen in der Schwangerschaft

A complete spectrum of maternal liver diseases occurs during pregnancy. Many, such as viral hepatitis, are not related to pregnancy. In contrast, women may develop potentially life-threatening liver diseases uniquely related to pregnancy. Beside the syndrome of Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP syndrome), these include the common intrahepatic cholestasis of pregnancy and the very rare acute fatty liver of pregnancy. During the past decade the molecular pathogenesis of these two diseases has been better defined, and mutations in genes encoding the hepatocanalicular phospholipid transporter and enzymes of fatty acid β-oxidation have been identified as genetic risk factors. Furthermore, due to optimized obstetric, intensive care and hepatological management, maternal and fetal mortality have decreased significantly.     

Severe jaundice during pregnancy

Severe jaundice during pregnancy is exceptional; it rapidly compromises the maternal and fetal prognosis. The series of seven cases presented in this study (3 acute viral hepatitis, 3 acute steatosis of pregnancy, one uncertain diagnosis), demonstrates the rapid evolution and the major repercussion on the pregnancy (5 premature deliveries, four fetal deaths in 8 children). No maternal death occurred but the complications were practically constant (4 severe haemorrhages, 3 acute renal insufficiencies, one encephalopathy with convulsions). This study permits also to emphasize the difficulty of the diagnosis in the acute phase: laboratory tests are often not very significant and the needle biopsy of the liver is usually contra-indicated; a liver scan (3 cases) may be an interesting alternative. The treatment requires a collaboration between obstetrician and anesthetist. The obstetrical management rests on the condition of the fetus and the etiology since the current tendency is to deal rapidly with the pregnancy, in the presence of an Acute Steatosis.     

Hepatitis B and C in pregnancy

In general, pregnancy does not influence the course of hepatitis B (HBV) and C (HCV) infection. Most neonates born to mothers who suffer from acute viral hepatitis B and C are asymptomatic. Chronic hepatitis B and C infections can be transmitted to neonates. This route of transmission of HBV is a major contributing factor to the high carrier rate in endemic countries where 80–95% of infants born to HBsAg/HBeAg-positive (hepatitis B surface antigen and hepatitis B e antigen respectively) mothers are infected. Despite the availability of a immunoprophylactic vaccine, 10–15% of these infants are still infected. The possible reasons for vaccine failure include the ability of HBV antigens to induce immunotolerance and the existence of HBV variants. The factors contributing to vertical transmission of HBV and HCV are also discussed. These factors include viral load, virus variants and sensitivity of diagnostic tests. The rate of vertical transmission of HCV of less than 5% is lower compared to HBV in HCV-ribonucleic-acid-positive mothers. However, the risk of HCV transmission is increased to about 23% if the pregnant women are also human immunodeficiency virus (HIV) positive.