Editorial Board: Emmet B. Keeffe, MD (Chair);

Anna Lok, MD; Brian McMahon, MD; Albert Min, MD; Myron Tong, MD; Naoky Tsai, MD; Bruce Tung, MD

HBV Watch™

Timely Information for Practicing Physicians

 

December 2003

 

perinatal transmission of HBV

Topic Review: Antiviral therapy for prevention of perinatal HBV transmission.  Perinatal transmission of HBV still occurs despite the administration of hepatitis B immune globulin (HBIG) and hepatitis B vaccine to children born of HBV carriers. It remains unknown whether or not antiviral therapy in the third trimester of pregnancy, which probably has a low risk of adverse fetal effects, is effective in reducing the risk of HBV perinatal transmission, as available data are limited. In one study (van Zonneveld et al. J Viral Hepatitis 2003;10:294.), 8 highly viremic (HBV DNA ³ 1.2 x 109) mothers were treated with lamivudine 150 mg daily during the last month of pregnancy, in addition to passive-active immunization of the children at birth, and were compared with 24 mothers whose children were treated with passive-active immunization alone. One of 8 children (12.5%) in the group treated with lamivudine was HBsAg and HBV DNA positive at 12 months of age compared with 7 of 25 (28%) in the untreated group. The rate of perinatal infection in untreated patients in this study was unusually high compared with a 5% rate of infection seen in most studies. In a report by Kazim et al (Lancet 2002;359:1488.), HBV infection occurred in a child born of an HBsAg carrier in spite of HBV DNA suppression with lamivudine to undetectable levels in the mother. Thus, the role of antiviral therapy in preventing perinatal transmission is unknown and warrants a randomized study.

 

Analysis of HBV DNA levels and HBeAg titers in Chinese mothers and their babies.  Perinatal transmission is the major cause of chronic HBV infection in China. Zhanhui Wang and associates evaluated HBV serological markers in 95 HBsAg-positive pregnant women and their babies at birth and at 6 and 12 months of age.  Despite dual immunoprophylaxis with HBIG and HBV vaccination, 7.4% of the babies (7/95) were infected with HBV (HBV DNA+) during the first year after birth.  PCR analysis revealed that all babies had the same HBV DNA surface gene fragment sequences as their mothers.  In addition, 70% of babies from HBeAg-positive mothers (23/33) were HBeAg positive at birth compared with 0% of babies born to HBeAg-negative mothers (0/21).  Among 19 HBeAg-positive babies without persistent HBV breakthrough infection, HBeAg was cleared from the serum within 6 months in 17 babies and within 12 months in the remaining 2 babies.  These data show that perinatal transmission of HBV infection may occur despite dual immunoprophylaxis with HBIG and HBV vaccination and that HBeAg can cross the human placenta but clears in most babies by 6 months.  (Wang Z et al. J Med Virol 2003;71:360-366.)

 

LIVER TRANSPLANTATION (LTx)

Adjuvant hepatitis B vaccine.  HBV-related liver disease is the indication for LTx in 10%-20% of transplant patients, and posttransplant HBV reinfection can be prevented in most patients by use of HBIG.  Previous studies of active immunization with standard HBV vaccines have shown conflicting results.  Ulrich Bienzle and colleagues now report early results from a Phase I study that utilized an HBV vaccine formulated with the new adjuvants 3-deacylated monophosphoryl lipid A (MPL) and Quillaja saponaria (QS21).  Two groups of 10 liver transplant recipients on continuous HBIG therapy who were HBsAg positive and HBV DNA negative before LTx, and had been followed for at least 2 years post-LTx, were immunized with different concentrations of HBsAg and the new adjuvants (group I: 20 µg HBsAg, 50 µg MPL, 50 µg QS21; group II: 100 µg HBsAg, 100 µg MPL, 100 µg QS21).  Patients remained on HBIG and were vaccinated at weeks 0, 2, 4, 16, and 18.  Additional vaccinations were administered to patients who did not reach an anti-HBs titer > 500 IU/L.  Eight patients in each group (80%) developed high anti-HBs titers (group I: median, 7,293 IU/L [range, 721-45,811 IU/L]; group II: median, 44,549 IU/L [range, 900-83,121 IU/L]) and had discontinued HBIG for a median follow-up time of 13.5 months (range, 6-22 mo).  The vaccine was well tolerated.  The preliminary results of this small trial, which require confirmation, show that most patients immunized with the new vaccine developed protective antibody titers and were able to stop HBIG immunoprophylaxis.  Whether these results can be applied to patients with detectable HBV DNA before LTx and to those who are within the first 1-2 years post-LTx remains to be determined.  (Bienzle U et al. Hepatology 2003;38:811-819.)

 

Outcomes of HCV antibody-positive (anti-HCV+) and hepatitis B core antibody-positive (anti-HBc+) grafts.  The scarcity of donor grafts has resulted in an increased use of marginal liver grafts.  Sammy Saab et al analyzed outcomes in 377 patients who underwent LTx for hepatitis B or hepatitis C or received with anti-HBc+/anti-HCV+ grafts.  Five-year posttransplantation patient and graft survival rates were similar for hepatitis B patients who received anti-HBc+ compared with anti-HBc- grafts.  Similarly, patient and graft survival rates were similar for hepatitis C patients who received anti-HCV+ compared with anti-HCV- grafts.  In addition, the 5-year patient and graft survival rates in 22 patients who received anti-HBc+/anti-HCV+ grafts (74% and 69%, respectively) were similar to those who received anti-HBc+ or anti-HCV+ grafts.  Among hepatitis B patients, dual HBV prophylaxis with HBIG and lamivudine was associated with higher patient and graft 5-year survival rates than those obtained with single or no prophylaxis (P < 0.01 and P = 0.02, respectively).  These results are consistent with previous studies reporting that patient and graft survivals were not affected by the use of anti-HBc+ or anti-HCV+ grafts, when used in hepatitis B and hepatitis C patients.  (Saab S et al. Liver Transpl 2003;9:1053-1061.)

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