Abstract
Viruses are small, non-living parasites, which cannot replicate outside a host cell.
Viruses are grouped according to their genetic material: DNA or RNA.
DNA viruses are mostly double-stranded while RNA viruses are single-stranded.
A virus injects its genetic information into a host cell and then takes control of the cell’s machinery. This process enables the virus to make copies of its DNA or RNA and make the viral proteins inside the host cell. A virus can quickly make multiple copies of itself in one cell, release these copies to infect new host cells and make even more copies. In this way, a virus can replicate very quickly inside a host.
Virology1
Viruses are small, non-living parasites, which cannot replicate outside a host cell.
Viruses are grouped according to their genetic material: DNA or RNA.
DNA viruses are mostly double-stranded while RNA viruses are single-stranded.
A virus injects its genetic information into a host cell and then takes control of the cell’s machinery. This process enables the virus to make copies of its DNA or RNA and make the viral proteins inside the host cell. A virus can quickly make multiple copies of itself in one cell, release these copies to infect new host cells and make even more copies. In this way, a virus can replicate very quickly inside a host.
DNA Viruses (Deoxyribonucleic Acid)
DNA is a molecule that contains the instructions it needs to develop, live and reproduce. DNA viruses use DNA as their genetic material. Some common examples of DNA viruses are parvovirus, papillomavirus and herpes virus. DNA viruses can affect both humans and animals and can range from causing benign symptoms to posing a very serious health risk.
DNA looks like a double helix and a twisted ladder.
RNA (Ribonucleic Acid)
Unlike DNA, RNA comes in a variety of shapes and types.
Common examples of RNA viruses: hepatitis C virus (HCV), Ebola, SARS, influenza, polio, measles and retrovirus human immunodeficiency virus (HIV).
Introduction
Viral hepatitis in pregnancy is the commonest cause of hepatic dysfunction and jaundice. The viruses resulting in hepatitis are hepatotoxic and include hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV) and hepatitis E virus (HEV).
Epstein–Barr virus and cytomegalovirus could also be the causative agents for hepatitis in rare cases.
Viral hepatitis caused 1.34 million deaths in 2015, a number comparable to deaths caused by tuberculosis and higher than those caused by HIV.2
In May 2016, the World Health Assembly endorsed Global Health Sector Strategy (GHSS) on viral hepatitis 2016–21. The GHSS calls for elimination of viral hepatitis as a public health threat by 2030 (reducing new infections by 90 per cent and mortality by 65 per cent).2
The hepatoviruses are quite divergent in their structures, epidemiology and routes of transmission, incubation period, clinical presentation, natural history and diagnosis. Prevention and treatment options are also different.
Hepatitis A (HAV)
Hepatitis A is an acute self-limiting illness and does not cause chronic infection. Hepatitis A virus can cause mild to severe disease. A very small proportion of people infected with hepatitis A could die from fulminant hepatitis.3 It is the second most common form of viral hepatitis in the United States.4 It is rarely life-threatening, with an estimated mortality of 0.3–0.6 per cent.5 Approximately 1.5 million new cases are reported annually. The true incidence might be higher as mild cases are not reported.5
Virology and Epidemiology
Hepatitis A virus is a non-enveloped RNA virus. The lack of lipid envelope makes it relatively hard and acid-resistant. It can remain infectious for weeks. Human beings are the important reservoir. Hepatitis A virus is highly prevalent in areas with poor sanitary conditions. High endemic areas include Africa, central Asian countries and South America, and low endemic areas include Europe, Canada and the USA.
Pathogenesis and Transmission
The oral route is the primary mode of transmission, usually through ingestion of contaminated foods, especially raw and undercooked shellfish and person-to-person contact. Hepatitis A virus replicates in the small bowel and liver after ingestion, and is excreted via bile through feces. It has a short viraemia period, with peak infectivity during the two weeks before onset of symptoms.
Fetal Implications of Hepatitis A
The incidence of acute hepatitis A infection in pregnancy was quoted as less than 1:1000 prior to the introduction of HAV vaccine.6
Mother-to-child transmission (MTCT) of hepatitis A is very rare.
Only few cases of intrauterine transmission following maternal infection in the first trimester have been reported. The transmission resulted in fetal peritonitis and was confirmed by the presence of hepatitis A immunoglobulin M in fetal blood obtained by trans-abdominal blood sampling of the fetal umbilical cord, performed under ultrasound guidance (cordocentesis).7
There is increased risk of miscarriage and preterm labour.
Neonatal Implications
Maternal infection in the third trimester of pregnancy may result in self-limiting neonatal cholestasis or asymptomatic neonatal infection.8
Most viral infections are not affected by pregnancy.
There have not been any reported maternal or fetal mortalities due to hepatitis A.
Breastfeeding should not be discouraged, and the child should be protected through administration of immunoglobulin or the inactivated vaccine.9
Prevention
Safe water supply, food safety, improved sanitation and hand washing, especially before handling food, are important for its prevention.
Vaccination and Passive Immunisation
The hepatitis A vaccine (HAVRIX, VAQTA) is the most effective way to combat the disease and should be considered for pregnant women and women of reproductive age before visiting HAV-endemic areas.
Hepatitis A vaccination (an inactivated (killed) vaccine). Two doses are needed for long-lasting protection. It is prepared from inactive virus and is considered safe during pregnancy.10
If a pregnant woman is exposed to hepatitis infection, passive immunisation with immunoglobulins within two weeks of exposure is safe in pregnancy.
0.02 mg/mL of immunoglobulin by single intramuscular injection provides protection for three months in 80–90 per cent of people.7
Clinical Presentation
The presentation in pregnant and non-pregnant women is the same:
1. Fever and chills
2. Anorexia, nausea and vomiting
3. Dark urine and pale stool
4. Jaundice and hepatomegaly
Most signs and symptoms resolve in three weeks.
Complications
About 7 per cent of patients can have complications like cholestasis, prolonged jaundice, pruritus and fever.
Fulminating hepatitis occurs in less than 1 per cent of cases.
Diagnosis
The specific diagnosis of acute hepatitis A is made by serology testing of the patient’s blood; anti-HAV immunoglobulin M (IgM) is diagnostic. Detection of IgG anti-HAV alone indicates past infection.
The liver enzymes like transaminases are classically elevated by 10–100 times the normal range.11
Treatment
The treatment of hepatitis A is supportive to maintain comfort and adequate nutrition.
Hospitalisation is indicated if patients develop severe disease with coagulopathy, encephalopathy or severe malaise and asthenia. Liver transplantation may be required in rare cases.
Hepatitis A is not an indication for caesarean section delivery. Delivery should be based on the obstetric conditions of the mother and baby.
Hepatitis B (HBV)
Hepatitis B is an infectious disease caused by hepatitis B virus. The infection can result in acute or chronic course. HBV accounts for 3.5 million chronic infections worldwide and approximately 1 million deaths due to hepatocellular carcinoma and cirrhosis.12
Virology and Epidemiology
Hepatitis B virus is a double-stranded DNA virus which infects the liver cells and belongs to the Hepadnaviridae family. It has a lipid envelope with antigen protein called hepatitis B surface antigen.
Hepatitis B has three antigens:
1. Hepatitis B s surface antigen (HBsAg) is detected in high levels during acute or chronic infection. The presence of HBsAg indicates that the person is infective. As a part of immune response, the body normally produces the anti-HBs antibodies. HBsAg is the antigen used to make hepatitis B vaccine.
2. The total hepatitis B core antigen (HBcAg) appears at the onset of symptoms in acute hepatitis B and persists for life.
3- Hepatitis B e-antigen or pre-core (HBeAg) is generally detectable in patients with a new acute infection; the presence of HBeAg is associated with higher HBV DNA levels and increased infectivity.
Serologic testing and measurement of several hepatitis B virus antibodies or a combination of markers are used to identify different phases of the individual:
Acutely infected: IgM anti-HBc positive, HBsAg positive anti-HBc positive
Chronically infected: IgM anti-HBc negative, HBsAg positive
Immune: HBsAg negative, anti-HBc IgG positive, anti-HBs IgG positive13
HBV is prevalent in areas of sub-Saharan Africa and East Asia where 5–10 per cent of the adult population are chronically infected. In the USA acute hepatitis B occurs in approximately 1 in 1000 pregnancies.13
Pathogenesis and Transmission
Transmission of HBV is through different routes: sexual contact, parenteral routes (intravenous (IV) drug users or exposure to blood products), or close personal contact with open cuts and wounds from an infected person.
The highest concentration of the virus is found in blood, but other body fluids like semen, saliva and cervical secretions also contain high viral titres.
In the newborn, it occurs through placental transmission.
It has a 30–180 day incubation period.
Presentation of Acute Infection
Most people do not experience any symptoms during acute infection; however, some people have acute illness with symptoms that last several weeks, including, fever, nausea, vomiting, anorexia, extreme fatigue, dark urine and abdominal pain.
On examination jaundice and hepatomegaly may be detected.13
Maternal Implications of HBV Infection in Pregnancy
The course of acute hepatitis in pregnancy:
Over 90 per cent of immune-competent pregnant women clear the infection and experience complete resolution after acute illness.
About 5 per cent of adults would develop chronic hepatitis B (persistence of HBsAg for more than six months).
Fulminant hepatitis might develop in 0.1–0.5 per cent of patients after acute HBV infection.
The long-term risks of chronic HBV infection are hepatocellular carcinoma and cirrhosis with liver failure.14
Acute viral hepatitis is the most common cause of jaundice in pregnancy.15 It is usually mild and not associated with increased mortality.15
Women with liver cirrhosis are at a higher risk of maternal complications including gestational hypertension, placental abruption and peripartum haemorrhage.
Fetal Implications of Acute Hepatitis
Because of its size, HBV does not cross the placenta. Most vertical transmission occurs during delivery.
The newborn baby’s chance of getting infection is 90 per cent if the pregnant woman is an HBV carrier and is also positive for HBeAg.
Approximately 25 per cent of infected infants will become asymptomatic and potentially infective chronic carriers.
Consequently, unless adequate prophylaxis is provided, the newborn is at high risk of developing a chronic HBV infection, with its known long-term complications.16
Acute or chronic infection with HBV is not associated with increased risk of congenital malformations or stillbirth.
However, the fetal prognosis is poor if the woman has liver cirrhosis:
○ Intrauterine growth restriction
○ Intrauterine infection
○ Premature delivery
○ Intrauterine fetal demise
Diagnosis
Acute HBV infection is characterised by presence of HBsAg immunoglobulin M (IgM) and antibody to the core antigen, HBcAg.
Treatment
Treatment of hepatitis B in pregnancy is supportive.
Indications of Antiviral Therapy
Consideration of antiviral therapy depends on high serum HBV DNA levels.
1. If the levels near delivery are persistently greater than 10 000 copies/mL
2. If a woman develops acute liver failure or protracted severe hepatitis17
If antiviral therapy is required, both tenofovir and lamvudine have been used safely in pregnancy.
The World Health Organization (WHO) recommends the use of oral treatment tenofovir and entecavir, because these are the most potent drugs to suppress HBV. The infant should receive HBV immunoglobulin in addition to HBV vaccine first dose at birth.
Safety of exposure to antiviral therapy comes from the Antiretroviral Pregnancy Registry (APR) and the Development of Antiretroviral Therapy Study (DART). Results of both studies seem to be assuring as the birth defects rate was 2.7 per cent, which compares favourably with the Centers for Disease Control (CDC) birth surveillance system.18, 19 [EL 1]
Antiviral therapy with lamivudine, tenofovir or telbivudine in the third trimester can decrease MTCT to less than 5 per cent.20
Vaccinating non-infected pregnant women is safe, but is generally recommended for women with high risk of exposure.
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