Lamivudine therapy during the second vs the third trimester for preventing transmission of chronic hepatitis B

Abstract

There are little data on the timing of initiating lamivudine therapy for preventing transmission of hepatitis B in highly viremic mothers. Between May 2008 and January 2015, we retrospectively enrolled mothers with HBV DNA >6 log copies/mL who received lamivudine during pregnancy, and we compared them to untreated mothers. The primary measurement was the vertical transmission rate. The secondary outcomes were the mothers' and infants' safety. Among 249 consecutive mothers enrolled, 66 and 94 received lamivudine during the second and third trimesters, respectively, and 89 were untreated. At delivery, maternal mean HBV DNA levels were significantly lower in mothers who received lamivudine (4.45 log vs 7.16 log copies/mL; P<.001). Lamivudine treatment was well tolerated. However, early treatment during the second trimester did not significantly increase the percentage of mothers achieving HBV DNA levels of <6 log copies/mL compared to those treated during the third trimester (98.5% vs 94.7%; P=.40). At the age of 28 weeks, the vertical transmission rates were significantly lower in the lamivudine-treated mothers vs in the untreated mothers (0% [0/160] vs 5.62% [5/89]; P<.001), but the rates were similar when comparing the two subgroups treated with lamivudine (0% [0/66] vs 0% [0/94], P>.05). The birth defect rates and mothers' and infants' adverse events were similar among the groups. Lamivudine treatment initiated in the second or third trimester for mothers with HBV DNA levels below 9 log copies/mL was equally safe and effective in preventing vertical transmission. Thus, lamivudine should be deferred until the third trimester to minimize foetal exposure and drug resistance.

Efficacy and safety of antiviral treatment on blocking the mother‐to‐child transmission of hepatitis B virus: A meta‐analysis

“…Of the 32 RCTs that enrolled 4189 pregnant women, 17 studies evaluated the effect of LAM, 15 studies evaluated LdT, 3 studies evaluated TDF, and 3 studies evaluated both LAM and LdT . Of the 27 non‐RCT studies enrolling 5039 pregnant women, 10 evaluated LAM, 18 evaluated LdT, 3 studies evaluated TDF, 2 evaluated both LAM and LdT, and another 2 studies evaluated both LAM and TDF . The characteristics of pregnant women and newborns in the 59 studies are summarized in Table .…”

An expert consensus for the management of chronic hepatitis B in Asian Americans

“… TDF should be considered as the first line treatment option for mothers with high viraemia and started at gestational week 30, or earlier if maternal liver disease required treatment. As the second line treatment, telbivudine may be used during pregnancy. LAM should be limited to late second trimester or third trimester treatment for patients with HBV DNA between 6 and 9 log 10 copies/mL due to the potential for resistance and lower potency …”

“…LAM should be limited to late second trimester or third trimester treatment for patients with HBV DNA between 6 and 9 log 10 copies/mL due to the potential for resistance and lower potency. 139,148 In a retrospective study by Pan et al, a significant reduction in the MTCT rate of HBV was observed in HBeAg positive mothers with high viral loads when elective caesarean section was performed. 149 However, further studies are warranted to confirm these findings.…”

Efficacy and safety of antiviral therapy for HBV in different trimesters of pregnancy: systematic review and network meta-analysis

“…Among the selected studies, 3 RCTs [7-9] and 12 non-RCTs [10,[16][17][18][19][20][21][22][23][24][25][26] compared treatment started in the third trimester versus control, 7 non-RCTs compared the timing of second trimester versus control [27][28][29][30][31][32][33], 3 non-RCTs compared first trimester versus control [14,34,35], 4 non-RCTs compared second and third trimester versus control respectively [11,[36][37][38], 3 non-RCTs compared first, second trimester versus control respectively [39][40][41]; 2 non-RCTs compared first, third trimester versus control respectively [12,42], 1 non-RCTs compared first, second trimester, third trimester versus control respectively [13]. No randomized controlled trials were conducted for the treatment that was applied during first or second trimester except for several non-RCTs.…”

“…Emerging data suggest the application of antiviral therapy in the third trimester is able to prevent immunoprophylaxis failure [7][8][9][10] to a great extent. Currently, only scarce studies showed the rates of MTCT appeared similar under the utilization of agents during second and third trimester [11], but the events of HBV transmission were still reported even if their mothers obtained a treatment in late pregnancy [12,13]. The well efficacy and safety in preventing MTCT have been clearly investigated among highly viremic HBV of mothers that started antiviral therapy in the first or second trimesters [12,14].…”