Tenofovir to Prevent Perinatal Transmission of Hepatitis B

Mother-to-child transmission of hepatitis B virus (HBV) accounts for the majority of cases of chronic HBV infection.  HBV infection affects more than 250 million people worldwide and in many cases results in cirrhosis or hepatocellular carcinoma.  As such, there has been interest in preventing perinatal transmission.

The most recent study (C Jourdain et al. NEJM 2018; 378: 911-23) again showed that tenofovir administration to pregnant women with HBV can prevent transmission.  This study enrolled 331 women.  Key findings:

  • 0% (0/147) infants in the tenofovir group developed HBV infection compared to 2% (3/147) in the control group. This did not reach statistical significance
  • The placebo group received HBV vaccination and hepatitis B immune globulin 1.2 hours and 1.3 hours after birth (median time).  This rapid provision of treatment along with completion of four doses of HBV vaccine likely helped keep the placebo group HBV infection rate low

In the related editorial (G Dusheiko. pg 952-3), it is noted that “current levels of evidence supporting antiviral therapy with TDF [tenofovir] (or possbily lamivudine or telbivudine) to reduce levels of maternal HBV DNA during pregnancy have been accepted by the” AASLD.

Related blog posts:

“Immune-tolerant” — a misnomer for HBV infection

When hepatitis B virus (HBV) infection occurs in the perinatal period, often the result is high levels of  HBV DNA yet immune-mediated damage of the infected liver is generally not observed and serum aminotransferases are normal.  This phase of infection has been considered “immune-tolerant.”  This phase can last for years or even decades.  New data indicate that the during this phase, there is preserved T-cell function and there are indications of good immune function (Gastroenterol 2012; 143: 637-45, & editorial 529-32).

The authors of the study isolated T cells from different age groups of patients with chronic HBV infection.  Then, they used flow cytometry methods to measure production of numerous cytokines.  In addition, markers of T-cell exhaustion or inhibition were examined.

Key Finding: young patients had more specific HBV-specific T cells with the ability to proliferate and produce cytokines than adult patients.

The study itself is highly technical with graphs of cytokine profiles, quantitation of T-cell expressing exhaustion markers, dot plots, etc.  Some of the figures are easy to understand like Figure 5 which plots the multifunctionality of HBV-specific response with three separate charts lined up; these correspond to “Immune tolerant,” “Chronic active,” and “Inactive carriers.”

The editorial is essential to understanding this study & restates the other findings:

  • “the authors found that T cells from CHB patients were more likely to produce TH1 cytokines …compared with those from healthy subjects”
  • they “found no global differences in this profile between tolerant and active states”
  • HBV-specific T-cell response: “a PD-1 high/CD127 low ‘exhausted’ phenotype were actually found to increase with age”
  • “T-cell responses to HBV core, envelope, and X proteins were readily observable in all patients”

The editorial speculates that so-called ‘tolerance’ may occur at a local/hepatic level, largely a ‘matter of sequestration.’  And, concludes that this study has “view-changing” observations.  Ultimately, this may lead to therapeutic treatments aimed at the liver microenvironment & may change our opinion of the suitability of treating younger patients.

More on perinatal HBV

In addition to a recent blog entry (How to stop HBV vertical transmission), several other recent articles add information about HBV vertical transmission:

  • Gastroenterology 2012; 142: 773-81.  Data from 2386 Taiwanese children born to HBsAg-positive mothers were examined.  HBeAg-positivity increased the likelihood of having an HBV-infected infant (9.26%) despite appropriate immunization & HBIG.  Since HBeAg-posiitivity is associated with higher HBV DNA levels, this is logical based on previous studies. Fulminant HBV developed in 1 of 1050 children who did not receive HBIG; in this study, the majority of mothers with HBeAg-negative HBV did not receive HBIG.
  • Pediatrics 2012; 129: 609-16.  This study examined HBV prevention in the U.S. from 1994-2008.  The CDC created the US Perinatal Hepatitis B Prevention Program (PHBPP) to accelerate progress at eliminating perinatal HBV transmission.  While the number of infants born to HBsAg-positive women with HBV increased from 19,208 to 25,600, the incidence of infants with chronic hepatitis B virus infection among tested infants decreased from 2.1% in 1999 to 0.8% in 2008.  This is due to the fact that 94.4% of PHBPP-managed infants received HBV vaccine and HBIG within 1 day of birth.  Yet, gaps remain.  The number of infants who completed the vaccine series by 12 months actually declined from 86% (1994) to 77.7% (2008). And, in 2008 only one-quarter of CDC’s 25,6000 infants born to HBsAg-positive women had known serologic outcomes.

Related previous post: Looking for trouble