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Commented Summary from Current Medical Literature |
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Efficacy and safety of Lamivudine for chronic hepatitis B
in pregnancy
Summary: In this study Su and their colleagues from main land China enrolled 38 pregnant women who had been receiving lamivudine due to chronic hepatitis B before conception and decided to continue that voluntarily during pregnancy. Twelve double antigens (HBsAg/HBeAg)-positive mothers were further evaluated. Their infants had received active and passive immunization at birth and followed-up for one year. None of the infants were positive for either HBsAg or HBeAg at the end of follow-up. Thus vertical transmission blocking rate was 100% in this group. Three groups of control pregnant women with chronic hepatitis B were selected from medical literatures. All cases were double antigens (HBsAg / HBeAg)-positive. Group one consisted of 81 pregnant women and the infants only received active immunization. The blocking rate of vertical transmission was 74%. In group two, 37 pregnant women were enrolled and the infants received active immunization with only minimal changes in dosages of vaccine comparing to the first control group. The blocking rate of vertical transmission was 64%. The third group consisted of 10 pregnant women. The infants received no medical intervention. The blocking rate of vertical transmission was zero in this group. In other words, natural vertical transmission of HBV from double antigens (HBsAg/HBeAg)-positive mothers to their infants were 100%. In this study, they concluded that using 100 mg lamivudine by pregnant women with chronic hepatitis B not only did not develop any serious side effect but increased blocking rate of vertical transmission in their infants.
Source: Su GG, Pan KH, Zhao NF, et al. World J Gastroenterol. 2004; 10: 910 – 912.
Comment: HBV infection is a global health problem. Around 300 million people have chronic hepatitis B worldwide. Vertical transmission is playing a major role in spreading of infection in areas with high frequency of the disease. By vertical transmission, we usually mean perinatal transmission of HBV during delivery or on the first few months after delivery and, therefore, intrauterine transmission has not been well appreciated in this process. Recently, however, this route of transmission has become an important part of vertical transmission. It appears that intrauterine transmission happens in the third trimester when the decidual tissue becomes thin enough to let passage of HBV and its antigens. Concentration of HBV and its antigen products were found higher in the maternal side of the placenta as compared to that of the fetal side.1, 2 On the other hand, there is no evidence that intrauterine viral transmission will not happen early in pregnancy. Regardless of the time of intrauterine transmission, to minimize the likelihood of vertical transmission, treating infected pregnant women is currently becoming a reality. We will be able to achieve this goal if we know what drug and when it should be administered.
Lamivudine has been used in combination with other nucleoside analogues to treat AIDS, over the last few weeks of gestation with no serious side effect. Toxicity of lamivudine, however, was demonstrated in mouse and rabbits with much higher dosage (60 – 1000 times).3 This drug can freely cross the placenta and accumulate in amniotic fluid.4, 5 At the moment, this drug is prohibited to be used in the first trimester of pregnancy.
There are three interesting points in this study: 1) no serious side effect of lamivudine was reported in pregnant women who have received this drug from the first day of gestation, 2) adding this modality to the routine passive and active immunization could prevent the rate of vertical transmission in all infants of mothers who are positive for both HBsAg/HBeAg antigens, and 3) normally vertical transmission occurs in almost 100% of double antigens (HBsAg/HBeAg)-positive mothers. Nonetheless, the following shortcomings are evident in this study: 1) small sample size; blocking rate of vertical transmission was concluded only from 12 mother-infant pairs, 2) duration of lamivudine therapy was unknown before conception, 3) there was no histopathological information on liver damage before starting the drug, 4) vertical transmission in infants was assessed only by measuring HBsAg and HBeAg quantitative measurement of HBV DNA was an important additional confirmatory test which has not been done, and 5) infants in control groups received only active immunization while 12 infants in the study group received both passive and active immunization. Therefore, the observed 100% blocking rate could partly be due to passive immunization.
Although vertical transmission is a major route of infecting new cases in areas with high prevalence of the disease (e.g. like China), this rule cannot be applied for regions where the disease is not prevalent. Result of a population-based study indicates that the prevalence rate of HBV in Iran is around 3%6 which means that we are living in a region with intermediate prevalence of the disease. Transmission of HBV in Iran, nevertheless, appears to be vertical. Thus, we must define what we mean exactly by saying “vertical transmission”. If it is meant to include the perinatal transmission, then we have to pay more attention to screening of pregnant women for HBV infection and to find out the best therapeutic modalities. Anyway, this part should not be ignored, or an ongoing intrauterine transmission will add on new infected cases to our society. These cases will have a high viral load, and will be immuno-tolerant and difficult-to-treat patients.
Ghodratallah Montazeri MD
Digestive Disease Research Center, Tehran University of Medical Sciences.
References:
1. Zhang SL, Yue YF, Bai GQ, Shi L, Jiang H. Mechanism of intrauterine infection of hepatitis B virus. World J Gastroenterol. 2004; 10: 437 – 438.
2. Xu DZ, Yan YP, Zou S, et al. Role of placental tissues in the intrauterine transmission of hepatitis B virus. Am J Obstet Gynecol. 2001; 185: 981 – 987.
3. Bishop JB, Tani Y, Witt K, et al. Mitochondrial damage revealed by morphometric and semiquantitative analysis of mouse pup cardiomyocytes following in utero and postnatal exposure to zidovudine and lamivudine. Toxicol Sci. 2004; 81: 512 – 517.
4. Johnson MA, Moore KH, Yuen GJ, Bye A, Pakes GE. Clinical pharmacokinetics of lamivudine. Clin Pharmacokinet. 1999; 36: 41 – 66.
5. Forestier F, de Renty P, Peytavin G, Dohin E, Farinotti R, Mandelbrot L. Maternal-fetal transfer and amniotic fluid accumulation of lamivudine in human immunodeficiency virus-infected pregnant women. Am J Obstet Gynecol. 2001; 184: 153 – 158.
6. Amini S, Mahmoodi MF, Andalibi S, Solati AA. Seroepidemiology of hepatitis B, delta, and human immunodeficiency virus infections in Hamadan Province, Iran: a population-based study. J Trop Med Hyg. 1993; 96: 277 – 287.