Chronic hepatitis B in pregnant women: Current trends and approaches

Table 1 Examination of pregnant women

	APASL 2016[8]	EASL 2017[9]	AASLD 2018[10]
All pregnant women	Pregnant female (preferably during the first trimester to vaccinate unprotected mothers) should be tested for HBV infection	Screening for HBsAg in the first trimester of pregnancy is strongly recommended	All pregnant women should be screened for HBV infection
Examination of HBsAg-positive women during pregnancy	Maternal HBeAg, HBV DNA status, and ALT level should be checked during pregnancy	ALT, HBV DNA level, and HBsAg level	ALT level, HBV DNA or imaging for HCC surveillance if indicated

APASL: Asia-Pacific Association Society for the Study of the Liver; EASL: European Association for the Study of the Liver; AASLD: American Association for the Study of Liver Diseases; HBV: Hepatitis B virus; HBsAg: Hepatitis B surface antigen; HBeAg: Hepatitis B e antigen; ALT: Alanine aminotransferase; HCC: Hepatocellular carcinoma.

Table 2 Prevalence of hepatitis B surface antigen among pregnant women

Ref.	Country	Years	Number	HBsAg-positive (%)
Kirbak et al[17], 2017	Republic of South Sudan	2013-2014	280	11
Fouelifack et al[18], 2018	Cameroon	2016	360	9.4
Bittaye et al[19], 2019	Gambia	2015	426	9.2
Tanga et al[20], 2019	South Western Ethiopia	2017	253	7.9
Kishk et al[21], 2020	Egypt	2018-2019	600	5
Fessehaye et al[22], 2018	Eritrea	2016	5009	3.2
Sheng et al[23], 2018	China	2016	14314	3.1
Cetin et al[24], 2018	Turkey	2016	475	2.1
Mishra et al[25], 2017	India	2016	3567	1.09
Biondi et al[26], 2020	Canada	2012-2016	651745	0.63
Lembo et al[27], 2017	Italy	2010-2015	7558	0.5
Ruiz-Extremera et al[28], 2020	Spain	2015	21870	0.42
Harris et al[29], 2018	United States	2011-2014	870888	0.14

HBsAg: Hepatitis B surface antigen.

Table 3 Clinical features and vertical transmission risk in different phases of chronic hepatitis B

Phase of CHB	ALT	Fibrosis (Metavir score)	HBV DNA level	Markers of HBV-infection	Vertical transmission risk
Phase of immune tolerance	Normal	F0	Very high (108-109 IU/mL)	HBsAg+; HBeAg+; HBeAb-; HBcorAb+	Very high
Immunoreactive phase	Elevated	F1-F4	High (106-107 IU/mL)	HBsAg+; HBeAg+/-; HBeAb-/+; HBcorAb+	High
Inactive carriage of HBsAg	Normal	F0	Less than 2000 IU/mL	HBsAg+; HBeAg-; HBeAb+; HBcorAb+	Low
Phase of HBeAg-negative CHB	Elevated	F1-F4	Middle (10³-107 IU/mL)	HBsAg+; HBeAg-; HBeAb+; HBcorAb+	Depends on HBV viral load
Occult CHB	Normal	F1-F4	+/-, HBV DNA in liver+	HBsAg-; HBeAg-; HBeAb-; HBcorAb+/-	Low

CHB: Chronic hepatitis B; ALT: Alanine aminotransferase; HBV: Hepatitis B virus; HBsAg: Hepatitis B surface antigen; HBeAg: Hepatitis B e antigen; HBeAB: Hepatitis B e antibody; HBcorAb: Hepatitis B core antibody.

Table 4 Treatment of pregnant women with chronic hepatitis B

	APASL 2016[8]	EASL 2017[9]	AASLD 2018[10]
Therapy	In pregnant females with chronic HBV infection who need antiviral therapy, tenofovir is the drug of choice for mothers indicated for antiviral treatment during the first through third trimester of pregnancy	Tenofovir is recommended for pregnant women with CHB and advanced fibrosis. Therapy with tenofovir should be continued, and if the woman was receiving other drugs, these other drugs should be replaced with tenofovir	Women who meet standard indications for HBV therapy should be treated. HBV-infected pregnant women with cirrhosis should be managed in high-risk obstetrical practices and treated with tenofovir to prevent decompensation
To prevent vertical transmission	For reduction of risk of mother-to-infant transmission that occurs during the perinatal period, short-term maternal NAs starting from 28 wk to 32 wk of gestation is recommended using either tenofovir or telbuvidine for those mothers with HBV DNA above 6-7 log10 IU/mL. Since, the HBV transmission could occur even with lower maternal HBV DNA level, NAs could be administered after discussion with the patient, even in patients with lower DNA level. The NA could be stopped at birth and when breastfeeding starts, if there is no contraindication to stopping NA	In all pregnant women with high HBV DNA level (> 200000 IU/mL) or HBsAg level > 4 log10 IU/mL, antiviral prophylaxis with tenofovir disoproxil fumarate should start at week 24-28 of gestation and continue for up to 12 wk after delivery	Women without standard indications but who have HBV DNA > 200000 IU/mL in the second trimester should consider treatment to prevent mother-to-child transmission

APASL: Asia-Pacific Association Society for the Study of the Liver; EASL: European Association for the Study of the Liver; AASLD: American Association for the Study of Liver Diseases; HBV: Hepatitis B virus; CHB: Chronic hepatitis B; NA: Nucleoside analogues; HBsAg: Hepatitis B surface antigen.

Table 5 Cessation of nucleoside analogues treatment after delivery

APASL 2016[8]	EASL 2017[9]	AASLD 2018[10]
Cessation of NA therapy (at delivery or 4-12 wk after delivery) is recommended in females without ALT flares and without pre-existing advanced liver fibrosis/cirrhosis. Continuation of NA treatment after delivery may be necessary according to maternal liver disease status	If NA therapy is given as prophylaxis, i.e., only for the prevention of perinatal transmission, its duration is not well defined (stopping at delivery or within the first 3 mo after delivery)	HBV-infected pregnant women who are not on antiviral therapy as well as those who stop antiviral at or early after delivery should be monitored closely for up to 6 mo after delivery for hepatitis flares and seroconversion. Long-term follow-up should be continued to assess need for future therapy

APASL: Asia-Pacific Association Society for the Study of the Liver; EASL: European Association for the Study of the Liver; AASLD: American Association for the Study of Liver Diseases; NA: Nucleoside analogues; ALT: Alanine aminotransferase.

Table 6 Hepatitis B virus prophylaxis in newborns

APASL 2016[8]	EASL 2017[9]	AASLD 2018[10]
HBIG and hepatitis B vaccine can be given to newborns from HBsAg-positive mothers immediately after delivery	The combination of HBIG and vaccination is administered within 12 h of birth	HBIG and HBV vaccine should be administered to the newborn < 12 h after delivery

APASL: Asia-Pacific Association Society for the Study of the Liver; EASL: European Association for the Study of the Liver; AASLD: American Association for the Study of Liver Diseases; HBIG: Hepatitis B immunoglobulin; HBsAg: Hepatitis B surface antigen; HBV: Hepatitis B virus.

Table 7 Breastfeeding of newborns

APASL 2016[8]	EASL 2017[9]	AASLD 2018[10]
Breastfeeding is not recommended while the woman is receiving antiviral therapy	Breastfeeding is not contraindicated in women not receiving antiviral therapy and during treatment with tenofovir	Breastfeeding is not prohibited for women with or without antiviral therapy

APASL: Asia-Pacific Association Society for the Study of the Liver; EASL: European Association for the Study of the Liver; AASLD: American Association for the Study of Liver Diseases.