Management of hepatitis B virus infection in patients with inflammatory bowel disease under immunosuppressive treatment

Table 1 Studies investigating hepatitis B virus prevalence in inflammatory bowel disease patients

Ref.	Type of study; Country	Patients	HBsAg-positive	Anti-HBc-positive	Anti-HBs-positive	Comments
Losurdo et al[33], 2020	Single-center cohort; Italy	807 IBD	0.9%	7.7%		Similar to regional prevalence
		438 CD
		369 UC
Fousekis et al[31], 2019	Retrospective single-center; Greece	602 IBD	5.3%	13.4%	32.4%	Similar to regional prevalence
Silva et al[94], 2019	Cross-sectional; Brazil	306 IBD	0.7%			Similar to regional prevalence
		165 UC
		141CD
Chou et al[95], 2019	Retrospective; Taiwan	190 IBD	13.3%			Higher prevalence of HBsAg in IBD
		80 CD
		110 UC
Yeo et al[96], 2018	Prospective cohort; Korea	210 IBD	3.8%	26.2%		Treatment-naïve similar prevalence
		109 UC
		101 CD
Chen et al[35], 2017	Retrospective; China	980 IBD	7.9%	41.2%	46.6%	Higher prevalence of HBsAg in IBD
		334 UC	8.1%	52.7%	48.8%
		646 CD	7.7%	35.3%	45.5%
Harsh et al[34], 2017	Retrospective; India	908 IBD	2.4%			Similar to regional prevalence
		581 UC	2.2%
		327CD	2.8%
Waszczuk et al[32], 2016	Prospective cross-sectional; Poland	147 IBD		14.3%		Similar to regional prevalence
Chan et al[97], 2016	Retrospective cohort; China	406 IBD	5.7%			Similar to regional prevalence
He et al[98], 2015	Retrospective; China	449 CD	13.6%	25.4%	31.2%	Similar to regional prevalence
		226 UC	16.8%	30.1%	24.3%
Ben Musa et al[47], 2014	Retrospective observational; United States	500 IBD	1.8%	3.2%		Similar to regional prevalence (screening rate 51%)
Huang et al[99], 2014	Retrospective; China	714 IBD	5.5%	40.6%	21.6%	Higher prevalence of HBsAg in IBD patients
Kim et al[37], 2014	Observational; Korea	513 IBD	3.7%			Similar to regional prevalence
		241 CD	4.1%
		272 UC	3.3%
Papa et al[28], 2013	Prospective; Italy	301 IBD	0.3%	7.3%		Similar to regional prevalence
Park et al[93], 2012	Retrospective; Korea	4153 IBD	4.1%			Similar to regional prevalence
		1521 CD	3.6%
		1728 UC	4.6%
Katsanos et al[30], 2010	Retrospective; Greece	482 IBD	2.3%			Similar to regional prevalence
Chevaux et al[100], 2010	Hospital-based; France	315 IBD			48.9%	Similar to regional prevalence
		252 CD	0.8%	2.8%
		63 UC	1.6%	1.6%
Loras et al[101], 2009	Multicenter Hospital-based; Spain	2076 IBD				Similar to regional prevalence
		1128 CD	0.6%	7.1%	17%
		928 UC	0.8%	8%	14.9%
		20 IC	0	5.3%	17.6%
Tolentino et al[27], 2008	Hospital-based; Brazil	102 CD	0	43.3%		Higher prevalence of anti-HBc patients
		74 UC	2.3%	56.7%
Esteve et al[102], 2004	Multicenter; Spain	80 CD	7.5%			Screening prior to anti-TNF treatment
Biancone et al[26], 2001	Multicenter; Italy	332 CD	2.1%	10.9%	14.4%	Higher prevalence of HBsAg in IBD
		162 UC	0.6%	11.5%	15.8%

CD: Crohn’s disease; HBc: Hepatitis B core protein; HBs: Hepatitis B surface protein; HBsAg: Hepatitis B surface antigen; IBD: Inflammatory bowel disease; TNF: Tumor necrosis factor; UC: Ulcerative colitis.

Table 2 Serologic profiles after initial screening

	HBsAg	Anti-HBc	Anti-HBs
Susceptible	Negative	Negative	Negative
Immune due to vaccination	Negative	Negative	Positive
HBV infection	Positive	Positive	Negative
Resolved HBV infection or occult HBV infection	Negative	Positive	Positive or negative

HBc: Hepatitis B core protein; HBs: Hepatitis B surface protein; HBsAg: Hepatitis B surface antigen; HBV: Hepatitis B virus.

Table 3 Available vaccines

	Company	Antigen - Adjuvant	Posology	Dosing
Engerix-B®	GlaxoSmithKline	Rec. major S Ag (yeast) Aluminum	1 mL	3- or 4-dose
			20 mcg	0-1-6 mo
				0-7 d-21 d-12 mo
HBVaxPRO®	Sanofi-Pasteur MSD	Rec. major S Ag (yeast) Aluminum	1 mL	3- or 4-dose
			5 mcg	0-1-6 mo
			10 mcg	0-1-2-12 mo
			40 mcg
Fendrix®	GlaxoSmithKline	Rec. major S Ag (yeast) Aluminum + 3-O-desacyl-4 - monophosphoryl lipid A	0.5 mL	4-dose
			20 mcg	0-1-2-6 mo
Heplisav-B®	Dynavax	Rec. major S Ag (yeast) HepB-CpG ligand	0.5 mL	2-dose
			20 mcg	0-1 mo
Twinrix®	GlaxoSmithKline	In.HAV + Rec. major S Ag (yeast) Aluminum	1 mL	3-dose
			720/20 mcg	0-7-21 d
				0-1-6 mo
Sci-B-Vac®	VBI Vaccines	Major S Ag, minor pre-S1 + pre-S2 Ag (mammalian cell) Aluminum	1 mL	3-dose
			10 mcg	0-1-6 mo
Pediarix®	GlaxoSmithKline	DTaP + inactivated poliovirus + Rec.S (yeast) Aluminum	0.5 Ml	3-dose
			10 mcg	(6-8 wk interval)

Ag: Antigen; DTaP: Diphtheria-tetanus-whooping cough (pertussis); In.HAV: Inactivated hepatitis A virus; Rec.: Recombinant.

Table 4 Revaccination studies for hepatitis B virus in inflammatory bowel disease

Ref.	Study	Patients, n	Strategies	Response rate for anti-HBs
Pratt et al[71], 2019	Retrospective cohort	149	3-dose schedule vs 1 or 2 doses	62.9%
				40.2% (> 10)
Cossio-Gil et al[60], 2015	Retrospective cohort	53	3-dose schedule	52.8%
Loras et al[59], 2014	Prospective	389	Double-dose 0-1-2	31.3% (> 100)
				44.4% (10-100)

HBs: Hepatitis B surface protein.