|Year : 2004 | Volume
| Issue : 1 | Page : 199-209
|Hepatitis B virus infection in pregnancy
Narendra Prasad Bohidar
Consultant Gastroenterologist, South Eastern Railway Hospital, Garden Reach, Kolkata, India
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|How to cite this article:|
Bohidar NP. Hepatitis B virus infection in pregnancy. Hep B Annual 2004;1:199-209
India falls into the intermediate endemicity area as regards the prevalence of HBV infection, which is 4%. Vertical and horizontal transmission in the perinatal period and early childhood are the major ways of propagation of this infection in India. To have control over these modes of transmission we need to have proper idea of HBV infection in pregnancy.
Thus, knowledge of HBV infection in pregnancy is important to us in view of:
a) the morbidity and mortality of the host (pregnant woman).
b) its effect on the process of parturition.
c) its capability to transmit the infection to an altogether new generation (foetus) and thereby increase the pool size.
Prevalence of HBV infection in pregnancy
There are a large number of studies from India showing the seroprevalence of HBV infection in pregnancy by testing for the presence of HBsAg. The presence of HBeAg in the HBsAg positives has also been looked into to know the replicative status (highly infective). The overall seropre-valence of HBV infection in pregnancy is not significantly different from the general population.
Manifestation in the host and management
This can be either an acute infection (which invariably occurs during pregnancy in a previously otherwise normal person) or a chronic infection (which is usually preexistent in either overt or latent form and pregnancy occurs later).
Hepatitis B infection does not have any special predilection for pregnancy., In a study on acute viral hepatitis in pregnancy from North India, HBV infection was observed in 19% and 18% of the pregnant and nonpregnant females respectively. Moreover, acute HBV infection is not more severe in pregnant women than in non pregnant individuals.,
The presentation, as a rule, does not differ from that in non pregnant women. Persons with overt acute viral hepatitis initially have non specific complaints including fatigue, malaise, anorexia, nausea, headache, myalgia and low grade fever. The nausea and vomiting of prodromal stage may be confused with the symposis present in pregnancy without hepatitis. If the illness resolves before there is sufficient liver cell injury and consequent secondary dysfunction to cause jaundice, these prodromal symptoms are passed off as a flu like viral syndrome or even for the normal physiological effects of pregnancy itself. Otherwise, jaundice develops within 2 to 10 days of the prodrome. These patients may also complain of right upper quadrant discomfort and examination may reveal tender hepatomegaly. Splenomegaly is noticed in about 10% of cases. In the later stages of pregnancy, the abdominal examination for hepatosplenomegaly may be difficult. Most often jaundice and symptoms of liver disease resolve in 6 weeks. Some of them have a violent course resulting in fulminant hepatic failure with features of cerebral edema, coagulopathy, multiple organ system failure and a few others have a persistent course beyond 6 months to result in chronic hepatitis.
Acute hepatitis, particularly late in pregnancy, may induce premature labour, but this seems to have little adverse effect on the foetus. Heiber et al have also noticed an increase in the incidence of prematurity (31.6%) over that seen in the general delivery population (10-11%). Apart from this, there are possibilities of intrapartum or postpartum hemorrhage especially if the prothrombin time is prolonged as in fulminant hepatic failure. Usual hematologic examinations are unremarkable. The aminotransferases are high even if the bilirubin is normal (as in anicteric hepatitis). The viral markers like HBsAg and IgM Anti-HBc are helpful in diagnosing acute hepatitis due to HBV.
The management is similar to that for non pregnant states. The management, like in a non pregnant state consists of supportive measures like high calorie diet, bed rest and vitamins. If marked anorexia or vomiting is present hospitalization may be required for intravenous fluid administration. There is no recommended antiviral therapy for acute viral hepatitis.
Chronic hepatitis and cirrhosis
In most affected individuals, chronic viral hepatitis is asymptomatic either indefinitely or until there is sufficient liver damage for the patient to develop manifestations of end stage liver disease. Many cases of chronic viral hepatitis are therefore diagnosed after serum transaminase levels are incidentally noted to be abnormal. This commonly occurs, when an apparently healthy young woman becomes pregnant and consults an obstetrician. Apart from the abnormal transaminases, the other investigations are usually normal unless the liver disease is severe. The cases with severe chronic hepatitis are usually aware of the liver problem before deciding about conception. In cirrhotics, the situation is slightly different; fertility is decreased probably due to amenorrhea and non ovulating cycles, and hence pregnancy is less often seen in them.
Physical examination may be normal or the patient may have subtle physical findings consistent with early cirrhosis, including palmar erythema, splenomegaly, and a small liver (sometimes with enlargement of the left lobe). Palmer erythema if present may be confused with that of pregnancy (physiological). Examination of the abdomen is difficult and may be ambiguous in the later stages of pregnancy when the liver and spleen are not palpable. In a minority of patients with end stage liver disease, clinical features of liver failure gradually becomes apparent and may be mistaken for a hepatic complication of pregnancy.
Chronic HBV carriers usually have normal pregnancies, unless there is severe chronic hepatitis or secondary cirrhosis and associated complications. Infeld et al had reported pregnancies in at least 28 of mild chronic hepatitis patients without any harmful maternal effects.
In cirrhotics, the main maternal risk is related to the degree of portal hypertension and the likelihood of esophageal variceal hemorrhage., Onset of labour increases the intraabdominal pressure thereby increasing the chances of variceal bleeding. Besides this, the deterioration of hepatic function also occurs. Liver and renal failure are the other causes of maternal mortality.
Supportive management of liver disease is similar to that in the non pregnant state. There are no dietary restrictions unless cirrhosis with complications has set in. Management of esophageal varices needs special attention by way of prophylactic banding. Use of pharmacoprophylaxis for bleeding requires very careful monitoring of the haemodynamic status. Coagulopathy should be managed with administration of fresh frozen plasma.
Antiviral therapy is considered as applicable to nonpregnant states. Of the three recommended available drugs for chronic hepatitis B, Interferon alpha is not used possibly due to lack of adequate controlled studies even though reports of its use in HCV infection does not not show significant interferon related fetal malformation., The safety of Adefovir Dipivoxil in pregnancy has not been clearly established. Only Lamivudine has been found to be safe and has been advocated for use in pregnancy. It is used in an oral dose of 100 mg daily.
This implies transmission of the hepatitis B virus from mother to infant. The significance of HBV infection during pregnancy derives in major part from its potential to be transmitted vertically. Ten percent of infants born to women with acute HBV infection during the first trimester of pregnancy are HBsAg positive at birth and 80 to 90% of neonates become HBsAg postive without prophylaitic therapy if acute maternal infection develops during the third trimester of pregnancy., This variable rate of vertical transmission from mothers with acute disease is explained by the fact that the placenta is a reasonably effective barrier to the spread of HBV infection. According to Okada et al, 85% of neonatal HBV infections are caused by intrapartum exposure to infectious blood and vaginal secretion, and the remaining 15% by haematogenous transplacental viral spread. However Zhang in 2004 showed by measuring concentration of HBsAg & HBcAg in maternal decidual cells, trophoblastic cells, villous mesenchymal cells and villous capillary endothelial cells that the main route of HBV transmission from mother to fetus is transplacental, from the mother's side of placenta to the fetal side. He also detected HBV DNA in amniotic fluid samples and vaginal secretion samples - emphasizing transmission of infection by these during parturition.
Okada et al examined the newborn infants of 139 asymptomatic carriers and did not find HBsAg positivity in the cord blood at any of them. However, on follow up for more than seven months, eight of the 11 mother child pairs tested showed antigenemia, the earliest appearing 5 days after delivery. The subtype of HBsAg was identical for each mother-child pair. In the true sense, this could be an instance of horizontal transmission from the mother during the immediate post natal period. Subsequently Okada et al in 1976 showed that all babies born to e antigen positive mothers developed surface antigenemia and in contrast, all of the babies born to e antibody positive mother escaped surface antigenemia. From this it is quite clear that e antigen positivity in the mother is a reliable marker to predict transmission of infection from mother to child.
In the absence of appropriate prophylaxis, 40% of the neonates of HBe antigen negative mothers and 90% of the neonates of HBe antigen positive mothers will develop HBV infection., However Sinatra et al reported that three infants born to anti-HBe positive mothers developed acute icteric hepatitis B within 3 months of birth.
Liu et al have demonstrated that HLA-DR3 is positively correlated with chronic HBV carriage and highly replicative status in pregnant women. HLA-DR13 correlated negatively with chronic HBV carrying of the pregnant women.
The strong possibility of vertical transmission lends importance to diagnosing acute or chronic HBV infection in pregnant women and justifies mandatory antepartum serum HBsAg screening. By doing so, previously unsuspected chronic HBV infection is diagnosed in young otherwise healthy individuals. This has the added benefit of making it possible to refer them for appropriate antiviral therapy before development of significant liver damage and associated functional insufficiency.
The infants of potentially infectious mothers are treated with HBV Human Hyperglobulin (HBIG) at delivery and simultaneously active immunoprophylaxis is initiated [Table - 2]. This approach is effective in preventing chronic HBV in approximately 85% neonates; it is ineffective in cases of hematogenous transplacental infection (15%).
Different measures have be a adopted to modify (interrupt) the vertical transmission of HBV infection:
HBIG - Administration of HBIG in a dose of 200 IU i.m. every week from 28th week of gestation reduces the intrauterine infection to 16.1% against 32.7%(in controls).
Lamivudine - It has been used with good safety and efficacy in the last four weeks of pregnancy to decrease the risks of vertical transmission. Li et al in 2003 showed that the intrauterine infection was reduced to 16.3% against 32.7% (controls) with its use from 28th week of gestation in a dose of 100mg/day. There are other studies too to substantiate this. However, there is a report of failure of vertical transmission of hepatitis B virus despite antenatal lamivudine therapy. Of course, in this case the authors detected precore mutant in both the mother and the child and this is to be interpreted appropriately without undermining the vertical transmission lowering effect of lamivudine.
Caesarean-section does not show any extra reduction in the incidence of immunoprophylaxis failure in comparison to vaginal delivery.
Other influences on the fetus
Apart from vertical transmission, the maternal HBV infection does not have any effect on the fetal outcome. Although there was an increase in incidence of prematurity, it had no effect on congenital malformations, stillbirths, abortions or intrauterine malnutrition in comparison to the controls.
Breast feeding is an important outcome of pregnancy and successful delivery. So, once the HBV infected mother with all possible precautions delivers a baby without any evidence of infection at birth, the next question about comes to mind is: whether breast feeding can be done safely? Even though, breast milk of infected mother contains HBV DNA, with appropriate immunoprophylaxis, including hepatitis B immunoglobulin and hepatitis B vaccine, breast feeding of infants of chronic HBV carriers (irrespective of replicative status) poses no additional risk for the transmission of the hepatitis B virus.
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Narendra Prasad Bohidar
Consultant Gastroenterologist, South Eastern Railway Hospital, Garden Reach, Kolkata
[Table - 1], [Table - 2]
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