| Hepatitis B virus （HBV） infection remains to be the major cause for liver diseasesaround the world. Nearly350and130million HBV carriers throughout the world are inChina, respectively. Hepatitis B virus is mainly transmitted by vertical transmission（mother-to-child transmission） and horizontal transmission （sexual transmission and bloodtransmission）. Mother-to-child transmission （MTCT） is identified as the major way oftransmission in china, which is30%～50％abroad. High maternal viremia （>106IU/ml） is akey factor correlated with MTCT, which has been confirmed by many studies. Lamivudineand telbivudine could sharply reduce the serum levels of HBV DNA, so both of them couldeffectively prevent MTCT. Telbivudine has potent and specific anti-HBV activity. So far,telbivudine had no mutagenic or carcinogenic effects and no appreciable embryonic or fetaltoxic effects, which are specialy relevant for women in their reproductive years. Compared toLamivudine, telbivudine had greater reduction of serum HBV DNA and lower drug resistance.Telbivudine for hepatitis B is classified as Food and Drug Administration （FDA） pregnancycategory B, which is used as a first-choice treatment for HBV vertical transmission. Atpresent, there are not enough data available regarding the efficacy and safety of telbivudinetreatment for chronic HBV infection, especially in pregnant women. The aims of our studywere to evaluate the effect and safety of telbivudine treatment in pregnant women withchronic hepatitis B （CHB） and high viral load during the second and third trimester ofgestation.However, MTCT of HBV immunoprophylaxis failure reaches up to39%through passiveor active immunization, the rate of which was controversial.The immunoprophylaxis failurerate of using lamivudine to prevent MTCT was18%. In our study the incidence of perinatal transmission in the untreated group was15.6%, but no case was found to be failure in HBVvertical transmission blockade by telbivudine till now. The reason for the significant viranceof failure rates between different therapies remains unclear. Despite by standardpassive-active immunoprophylaxis and antiviral treatment, HBV vertical transmission issupported to be correlated with high levels of maternal viremia, HBeAg positive, intrauterineinfection, or HBV mutation. Intrauterine infection is the main reason of immunoprophylaxisfailure and is the key point to prevent HBV MTCT. However, the mechanism of HBVintrauterine infection is still not clear. Several studies have confirmed that telbivudine couldinterdict vertical transmission effectively. In the study, we evaluated the effect and safety oftelbivudine treatment in pregnant women with CHB, investigated the change of serum HBVDNA, HBsAg and HBeAg of pregnancy after using telbivudine, and studied the mechanismof telbivudine to prevent MTCT. It has been demonstrated that HBeAg could cross the humanplacenta and reach the foetus circulation through the placenta, then the effect of immune cellsorganism to recognize and kill virus would be damaged and even affect the production ofspecialized antibody. Because of this the fetus cannot clear the hepatitis B virus coming fromthe maternal, further leading to chronic hepatitis B virus infection. Despite this conclusion hasnot been widely accepted, it supported the fact that the function of HBeAg in HBVintrauterine infection is more and more important.At present studies investigating the effects of Telbivudine to the transmission rateof HBsAg and HBeAg through placenta in the second and third trimesters of HBVinfected pregnancy hasn’t been reported yet. Our study researched the transmission rateof HBsAg and HBeAg by using quantitatively assay and further discuss the mechanism oftelbivudine-treatment to prevent HBV MTCT.Results:1. There were207cases in telbivudine group and152cases in the control group.123patients had detected the serum HBV DNA at delivery, the mean serum levels were3.52log10IU/ml, and25cases （20.3%） had undetectable HBV DNA. Median HBV DNA levelin69untreated patients was7.47log10IU/ml, there was no significamt difference betweenbaseline and delivery when regarding to the median serum HBV DNA levels.2. At the time of delivery, the ALT levels of those patients who had elevated ALT atbaseline in the two groups showed significant difference in our study （P=0.001）, the ALT levels of tebivudine-treated patients were lower than that in untreated patients. One monthafter delivery, the elevated ALT levels in treated group decreased to<5.21×ULN.3. There were211infants in telbivudine group and152infants in the control group. Theproportion of newborns with undetectable HBV DNA in cord blood was significantly higherin telbivudine-treated group than in untreated controls (163/165,98.8%vs.80/130,61.5%,respectively, P=7.708×10-17).4. When the infants were6months, the rate of serum HBsAg positivity intelbivudine-treated group was0%（0/180）, compared to15.6%（14/90） in untreated group（P<0.001）. At3months, among14HBsAg-positive infants,13were positive for HBeAg andHBV DNA and1infant was anti-HBc positive and HBV DNA positive （2.9log10IU/ml）. At6months, the data were similar to those at3month,13infants with HBeAg-positive still hadHBV DNA levels of more than6log10IU/ml.5. The incidence of adverse events in mothers with or without telbivudine showed nosignificant difference （P=0.429）. There were also no significant difference in prematuredelivery （P=0.167） and rate of postpartum hemorrhage in telbivudine-treated and untreatedpatients. The rate of spontaneous delivery in untreated mothers and in telbivudine-treatedmothers showed no difference as well （P=0.134）. At delivery, the median range of CKbetween two groups showed no significant difference （P=0.127）.6. The incidence of serious adverse events （SAEs） in infants in the treated and untreatedgroups was similar. There was no significant difference in weight, height, or Apgar scoresbetween two groups. One infant born to telbivudine-treated mother developed congenital cleftlip and palate （CLP） and died of serious complication at15days; another infant succumbed topulmonary hemorrhage mainly caused by hypoxia at1month. In controls, one pregnantwoman had a spontaneous delivery of dead twins at28weeks and5days of gestation; anotherinfant suffered from congenital ventricular septal defect.7.69pairs of maternal and infants in the telbivudine group and15pairs of maternal andinfants in the control group had detected serum HBsAg, HBeAg and anti-HBc. There were nosignificant differences in serum levels of HBsAg and HBeAg of telbivudine mothers atbaseline and delivery （P=0.167, P=0.102）. There were no significant differences in serumlevels of HBsAg, HBeAg and anti-HBc titers of the mothers from the telbivudine group andthe untreated group at delivery （P=0.058, P=0.065, P=0.727）.8. The serum HBsAg and HBeAg positive rate in the cordblood of telbivudine group were55.70%（39/70） and98.60%（69/70） respectively, compared to60.00%（9/15） and93.30%（14/15） in the control group. We demonstrated that the HBeAg was easier to transitthe placenta than HBsAg. The serum anti-HBc could absolutely transit the placenta in the twogroups.9. There were no significant differences in serum levels of HBsAg, HBeAg and anti-HBctiters of the cordblood in infants between the telbivudine group and the untreated group（P=0.761, P=0.225, P=0.924）. There was also no difference in the transmission rate ofHBsAg and HBeAg between two groups （P=0.172and P=0.163）. The transmission rate ofHBsAg and HBeAg ranged from0.02%～0.13%and1.00%～11.50%respectively. Thetransmission rate of HBsAg was lower than HBeAg (P=2.888×10-21).10. At12months none of the infants in telbivudine group infected HBV. The serumHBsAg and HBeAg disappeared within6months. At6months,1infant in the control groupwas positive for HBeAg and HBV DNA, all of the other infants were negative for HBsAg andHBeAg.12months the serum anti-HBc was positive as before.Conclusions:1. Telbivudine was effective and well-tolerated in HBeAg-positive pregnant women andtheir infants, and it was associated with significant reduction of vertical transmission of HBV.2. We demonstrated that telbivudine couldn’t effectivly downregulate the levels of serumHBsAg and HBeAg of the mothers and the transmission rate of cordblood in the telbivudinegroup. The mechanism of Telbivudine resulted mother to infant transmission blockade wasthat it could reduce the levels of HBV DNA.3. The transmission rate of HBsAg and HBeAg remains low and stable level, whichfollowing anti-HBc, HBeAg, and HBsAg. Detectable of the traditional cordblood HBVMarkers （HBsAg, HBeAg, and anti-HBc） could not be identified to diagnose the infection ofHBV.4. Exclude the infectious infant, our study demonstrated that the serum HBeAg was stillpositive at3months, but was disappeared at6months. Only the serum HBsAg is positive （orserum HBV DNA positive） after6months that could be determined to diagnose the infection. |
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