Clinical course of 161 untreated and tenofovir‐treated chronic hepatitisBpregnant patients in a low hepatitisBvirus endemic region

Abstract

Hepatitis B immunoprophylaxis failure is linked to high maternal viraemia. There is limited North American data on hepatitis B outcomes in pregnancy. Pregnant hepatitis B carriers were enrolled January 2011-December 2014 and offered tenofovir in the 3rd trimester if hepatitis B virus (HBV)-DNA was >7-log IU/mL. Outcomes were determined in treated vs untreated patients. In total, 161 women with 169 pregnancies (one twin, 170 infants; median age 32 years), 18% (29/161) HBeAg+ and median HBV-DNA 2.51 log IU/mL (IQR 1.66-3.65; range 0.8-8.1) were studied. 14.3% (23/161) received tenofovir due to high viral load (16/23, median 74 days, IQR 59-110) or due to liver disease (7/23). In 10/16 treated due to high viraemia, with confirmed adherence, follow-up HBV-DNA showed a 5.49 log decline (P = 0.003). In treatment naïve mothers, median alanine aminotransferase (ALT) increased from 17 IU/L (IQR 12-24) to 29 (IQR 18-36) post-partum (P = 1.5e-7). In seven highly viraemic mothers who declined therapy (HBV-DNA >8-log IU/mL); median ALT increased ~3X from baseline (P < 0.01). 26% (44/169) had Caesarean section with no difference in treated vs untreated subjects. No tenofovir-treated mothers had renal dysfunction. Data were available on 167/170 infants; in 50.8% (85/167) who completed immunoprophylaxis, 98.8% (84/85, including 12 exposed to tenofovir in utero) were HBV immune. One infant born to an HBeAg+ mother with HBV-DNA >8-log IU/mL failed immunoprophylaxis. In this prospective Canadian cohort study, most untreated mothers experienced mild HBV flares. Tenofovir in pregnancy is well tolerated and reduces viral load prior to parturition.

Efficacy and safety of tenofovir disoproxil fumarate in preventing vertical transmission of hepatitis B in pregnancies with high viral load

“…Five studies, including 4 observational studies 2, 3, 22, 23 and 1 RCT 8 , involving 585 pregnant women and 595 newborns, were included in the present meta-analysis. These very recent studies were published from 2013 to 2016; 2 studies were conducted in China 8, 23 , and another 3 studies were conducted in North American 22 , Australia 2 and Turkey 3 , respectively.…”

“…These very recent studies were published from 2013 to 2016; 2 studies were conducted in China 8, 23 , and another 3 studies were conducted in North American 22 , Australia 2 and Turkey 3 , respectively. The participants in all studies in the TDF group received 300 mg of TDF once daily, with a baseline HBV DNA level of > 7.7 (range, 7.7–8.28) log10 IU/mL, and an average baseline ALT level of 30.5 U/L.…”

“…The participants in all studies in the TDF group received 300 mg of TDF once daily, with a baseline HBV DNA level of > 7.7 (range, 7.7–8.28) log10 IU/mL, and an average baseline ALT level of 30.5 U/L. In 4 studies TDF treatment was initiated from gestational weeks 30–32 until 4–12 weeks following delivery 2, 8, 22, 23 , while in the remaining studies TDF treatment was initiated from gestational weeks 18–27 until 4 weeks following delivery 3 . The pregnant women in the control group in all studies did not receive antiviral therapy.…”

“…The pregnant women in the control group in all studies did not receive antiviral therapy. In 4 studies the investigators compared TDF versus control 3, 8, 22, 23 , while in 1 study researchers compared TDF versus LAM or control 2 . All infants in the included studies received a 3-dose HBV vaccination and hepatitis B immune globulin (HBIG) administration after delivery, and all mothers in these studies were instructed not to breast-feed their infants during the period in which they were receiving TDF treatment.…”

“…5, our analysis showed that infants born from pregnant women treated with TDF had a significantly lower vertical transmission rate compared to those born from the control group, as defined by infant HBsAg seropositivity at 4–12 months (5 studies, OR = 0.21, 95% CI = 0.07–0.61; P = 0.004), and TDF showed better improvement in reducing infant HBV DNA seropositivity at delivery (2 studies, OR = 0.16, 95% CI = 0.07–0.37; P = 0.000). TDF also significantly reduced the risk of infant HBV DNA seropositivity at delivery by 17.6%, and 1.36%-18% of newborns failed HBV immunoprophylaxis 2, 3, 8, 22, 23 in the control group.

Figure 5Forest plot showing meta-analysis of infant outcomes for studies comparing TDF versus control, based upon fixed-effects model.

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