Predicting Hepatitis B Vaccination Failure in Infants

A brief report (KW Cheung et al. Clin Gastroenterol Hepatol 2018; 16: 144-5) describes a prospective multicenter study (2014-16) in Hong Kong which examined immunoprophylaxis failure (IF) of infants (n=654) born to mothers infected with hepatitis B virus (HBV) infection.  All infants had received HBV vaccine and HBV immunoglobulin (within 12 hours of birth).  Maternal HBV DNA & serology was measured at 28-30 weeks.

Key finding:

  • There were 7 cases of IF (1.1%). All were born to women with positive HBeAg and HBV DNA >8 log10 copies/mL (>17 million IU/mL)
  • The authors note that “although a cutoff of 200,000 IU/mL (~6 log10 copies/mL) has been recommend, the optimal viral load cutoff to initiate HBV antiviral treatment remains debatable.”

My take: HBV prophylaxis with HBV vaccination and HBIG is very effective.  However, HBV DNA levels can be used to target HBV antiviral treatment to further minimize the chance of IF failure.

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Patient artwork

 

Antivirals Reduce Vertical Transmission of Hepatitis B

Chelsea Market, NYC

Chelsea Market, NYC

The latest study that shows antivirals interrupt hepatitis B viral (HBV) transmission from mother-to-infant: H-L Chen et al. Hepatology 2015; 62: 375-86.

In this open-label, non-randomized controlled study from Taiwan, the researchers recruited women to receive tenofovir (TDF) at a dose of 300 mg once a day (n=62), initiated from gestational age 30-32 weeks until 1 month following delivery, and compared them to a control group (n=56).  There were high levels of viremia with HBV DNA ≥7.5 log10 IU/mL. All infants received HBV vaccination and HBIG within 24 hours of birth.

Key findings:

  • Infant transmission of HBV was reduced: at 6 months of age, infant HBsAg positivity was 1.54% versus 10.71%, P=0.0481).  At delivery, HBV DNA positivity was noted in 6.15% compared with 31.48% of the control group.
  • Maternal ALT was improved in the TDF group. ALT elevation more than two times the upper limit of normal for ≥3 months occurred in 3.23% compared with 14.29% of controls.
  • Adverse effects: only mild to moderate (self-limited) gastrointestinal and skin symptoms were noted. No fetal abnormalities were identified.

Bottomline: Antivirals, including both tenofovir and telbivudine, reduce vertical HBV transmission with a favorable safety profile.  The use of antivirals is complementary to standard prevention which consists of providing Hepatitis B immune globulin and Hepatitis B vaccine to infants of HBV-infected pregnant women within 12 hours of birth.

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Hepatology Update -Summer 2014

Preventing Perinatal Transmission of Hepatitis B Virus (HBV): Hepatology 2014; 60: 468-76.  This nonrandomized study, conducted between 2009-2011 with approximately 700 patients, showed that the rate of perinatal transmission of can be brought down almost to zero by instituting therapy with either telbivudine or lamivudine in the third trimester of pregnancy.  The accompanying editorial (pgs 448-51) indicates that either telbivudine or tenofovir (both pregnancy class B agents with regard to teratogenicity) are preferred agents due to higher barrier to resistance. And, the article suggests starting as early as week 28 (especially if high viral HBV DNA load) and no later than 32 weeks gestation. Other recommendations from editorial include stopping antiviral after delivery in women who intend to breastfeed.

More on coffee: Hepatology 2014; 60: 661-69.  Coffee but not tea conferred protection from cirrhosis mortality.  “Compared to non-daily coffee drinkers, those who drank two or more cups per day had a 66% reduction in mortality risk.”  This study also had an accompanying editorial (pg 464-67) which reviews the biologic plausibility and potential mechanisms.

NASH pathology: Hepatology 2014; 60: 565-75.  The study describes a more precise way to categorize the diagnosis of nonalcoholic steatohepatitis (NASH) using the European Fatty Liver Inhibition of Progression (FLIP) pathology consortium proposal.  The diagnosis of NASH requires the presence of ballooning and lobular inflammation in addition to steatosis.  Using the FLIP approach, diagnosis concordance increased significantly.

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