Efficacy of maternal tenofovir disoproxil fumarate in interrupting mother‐to‐infant transmission of hepatitis B virus

Abstract

The efficacy and safety of maternal tenofovir disoproxil fumarate (TDF) in reducing mother-to-infant hepatitis B virus (HBV) transmissions is not clearly understood. We conducted a prospective, multicenter trial and enrolled 118 hepatitis B surface antigen (HBsAg)-and hepatitis B e antigen-positive pregnant women with HBV DNA 7.5 log 10 IU/mL. The mothers received no medication (control group, n 5 56, HBV DNA 8.22 6 0.39 log 10 IU/mL) or TDF 300 mg daily (TDF group, n 5 62, HBV DNA 8.18 6 0.47 log 10 IU/mL) from 30-32 weeks of gestation until 1 month postpartum. Primary outcome was infant HBsAg at 6 months old. At delivery, the TDF group had lower maternal HBV DNA levels (4.29 6 0.93 versus 8.10 6 0.56 log 10 IU/mL, P < 0.0001). Of the 121/123 newborns, the TDF group had lower rates of HBV DNA positivity at birth (6.15% versus 31.48%, P 5 0.0003) and HBsAg positivity at 6 months old (1.54% versus 10.71%, P 5 0.0481). Multivariate analysis revealed that the TDF group had lower risk (odds ratio 5 0.10, P 5 0.0434) and amniocentesis was associated with higher risk (odds ratio 6.82, P 5 0.0220) of infant HBsAg positivity. The TDF group had less incidence of maternal alanine aminotransferase (ALT) levels above two times the upper limit of normal for 3 months (3.23% versus 14.29%, P 5 0.0455), a lesser extent of postpartum elevations of ALT (P 5 0.007), and a lower rate of ALT over five times the upper limit of normal (1.64% versus 14.29%, P 5 0.0135) at 2 months postpartum. Maternal creatinine and creatinine kinase levels, rates of congenital anomaly, premature birth, and growth parameters in infants were comparable in both groups. At 12 months, one TDF-group child newly developed HBsAg positivity, presumably due to postnatal infection and inefficient humoral responses to vaccines. Conclusions: Treatment with TDF for highly viremic mothers decreased infant HBV DNA at birth and infant HBsAg positivity at 6 months and ameliorated maternal ALT elevations. (HEPATOLOGY 2015;62:375-386) D espite the 75%-90% reduction of chronic hepatitis B viral (HBV) infection following universal infant immunization, active/passive immunoprophylaxis has not eradicated mother-toinfant HBV transmission. [1][2][3][4] Approximately 10% of chronic HBV infections cannot be prevented.5-7 The major risks of chronic HBV infection in the immunization era are maternal hepatitis B surface antigen (HBsAg)/hepatitis B e antigen (HBeAg) positivity and high maternal viral load.5-9 Moreover, after immunoprophylaxis, children with HBV infection have a higher risk of developing hepatocellular carcinoma. 10,11 To achieve the goal of global eradication of HBV infection, better strategies aimed at interrupting Abbreviations: ALT, alanine aminotransferase; anti-HBs, antibody to hepatitis B surface antigen; D0, day 0, initiation of TDF treatment (baseline); D1M, 1 month after TDF treatment; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; P0, at partum; PXM, X months postpartum; SNR, signal-to-noise ratio; TDF, tenofov...

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

“…1 Among the last two agents, TDF should be preferred, because it has a better resistance profile and more extensive safety data in pregnant HBV positive women. 1,[196][197][198] In a woman of childbearing age without advanced fibrosis who plans a pregnancy in the near future, it may be prudent to delay therapy until the child is born. In a woman of childbearing age with advanced fibrosis or cirrhosis who agrees for a ''planned pregnancy'' in the future, PegIFNa therapy may be tried as it is given for a finite duration.…”

Acute Viral Hepatitis B with a Severe Clinical Course in Pregnancy: A Case Report

“…If the mother has high serum HBV DNA levels before the delivery, antiviral treatment should be considered to reduce viral load in the mother (13,14). Tenofovir disoproxil fumarate (245 mg/day) or lamivudine (100 mg/day) are recommended for antiviral treatment and both drugs can be used safely during pregnancy (9,15). Since the risk of resistance is low, tenofovir disoproxil fumarate should be preferred (16).…”

Management of special patient groups with hepatitis B virus infection: The EASL 2017 Clinical Practice Guidelines

“…Before initiating antiviral therapy for HBV infection, the pregnant woman and her spouse should be informed about the safety data of the HBV drugs. TDF should be preferred in these patients because it has an extensive safety profile and has a better resistance profile (15). There are no satisfactory data regarding the use of LAM, ADV and ETV.…”