Prophylactic managements of hepatitis B viral infection in liver transplantation

Table 1 Main results of published studies using combination therapy of low-dose hepatitis B immunoglobulin and nucleos(t)ide analogues and withdrawal of hepatitis B immunoglobulin from combination therapy

Ref.	Patients (n)	Median follow-up (mo)	NAs(dose)	HBIG protocol	HBV recurrence
Angus et al[34], 2000	32	18.4	32 LAM (100 mg/d)	400 IU or 800 IU/d im for 1 wk and then 400 IU or 800 IU/mo	1/32 (3.1%) HBsAg+
					0/32 (0%) HBV-DNA+
Gane et al[35],2007	147	62	147 LAM (100 mg/d)	400 IU or 800 IU/d im for 1 wk and then 400 IU or 800 IU/mo	5/147 (3.4%)
					actuarial risk of HBV recurrence was 1% at 1 yr and 4% at 5 yr
Karademir et al[36], 2006	35	16	33 LAM	6000 IU im intraoperatively, 2000 IU/d until HBsAb > 200 IU/L, and then 1200 to 2000 IU im on-demand if HBsAb < 100 IU/L, thereafter	2/35 (5.7%)
			2 LAM + ADV		Two HBV recurrent case had LAM resistance at LT
Iacob et al[38], 2008	42	21.6	42 LAM	10000 IU im in anhepatic phase and 10000 IU/d im for first 1 wk, and then 2500 IU im on-demand if HBsAb < 50 IU/L, thereafter	2/48 (4.8%)
Jiang et al[37], 2010	254	41.2	254 LAM	2000 IU im in anhepatic phase, followed by 800 IU/d for the next 6 d and weekly for the rest of 3 wk in the first postoperative month and 800 IU monthly or biweekly im on-demand if HBsAb < 100 IU/L, thereafter	14/254 (5.5%)
					The 1-, 3- and 5-yr HBV recurrence rates were 2.3%, 6.2% and 8.2%
					5 of 14 recurrent cases had YMDD mutants at recurrence
Nath et al[41], 2006	14	14.1	14 LAM + ADV	10000 IU HBIG iv in anhepatic phase and 10000 IU/d for first 1 wk, and then HBIG was withdrawn and replaced with oral ADV	1/14 (7.1%)
					HBV recurrent case showed normal liver function.
Angus et al[42], 2008	34	21	18 LAM + HBIG	Randomized trial	0/18 in HBIG + LMV
			16 LAM to LAM + ADV	All patients were treated with low-dose im HBIG + LMV ≥ 1 yr post-LT	1/16 (6.3%) in LMV + ADV (HBIG withdrawal group)
				18 patients continued HBIG vs 16 patients discontinued HBIG and ADV was added (LMV + ADV)	Recurrent case was HBsAg+/HBV-DNA-
Saab et al[43], 2011	61	15	19 LAM to LAM + ADV	All patients were treated with low-dose im HBIG + LMV ≥ 1 yr post-LT. All patients discontinued HBIG, and ADV or TDF was added as described left	2/61 (3.3%)
			41 LAM to LAM + TFV		Both recurrent case was HBsAg+/HBV-DNA- without liver dysfunction
			1 ETV to ETV + ADV

HBV: Hepatitis B virus; NAs: Nucleos(t)ide analogues; HBIG: Hepatitis B immunoglobulin; LT: Liver transplantation; HBsAb: Hepatitis B surface antibody; LAM: Lamivudine; ADV: Adefovir; ETV: Entecavir; TDF: Tenofovir disoproxil fumarate; im: Intramuscularly.

Table 2 Main results of published studies using vaccination after liver transplantation

Ref.	Patients (n)	Age, median (yr)	HBV-DNA negative before LT	Duration between LT and vaccination	Momo immunosuppression	Response to vaccination1	Vaccination protocol(dose:μg)
Sánchez-Fueyo et al[59], 2000	22	39	100%	33%	63.5	22.7%	40 im/40 im
							3 + 3 (/cycle)
							without HBIG
Angelico et al[60], 2002	17	53	100%	48%	100	11.8%	40 im/10 sc/40 im
							3 + 6 + 3 (/cycle)
							without HBIG
Bienzle et al[63], 2003	20	54	100%	78%	80	80%	20 im or 100 im
							5 + 3 (/cycle)
							with HBIG Adjuvant: MPL + QS21
Stärkel et al[64], 2005	10	49	90%	55%	100	40%	40 im/40 im
							5 (/cycle)
							with HBIG
							Adjuvant: MPL
Lo et al[66], 2005	52	47	81%	14%	92.3	1.9%	40 im
							3 + 3 (/cycle)
							without HBIG
Rosenau et al[62], 2006	8	50	37.5%	60%	37.5	12.5%	20 im
							6 (/cycle)
							without HBIG
Lo et al[66], 2007	20	52	80%	21%	85	35%	HBs + preS 20 im
							3 + 3 (/cycle)
							without HBIG
Tahara et al[69], 2009	20	53	75%	20%	60	65%	20 im or 40 im
							unrestraint
							with HBIG
							under immune-monitoring
Di Paolo et al[65], 2010	18	59	100%	73%	89	44%	20 im
							6 + 6 (/cycle)
							HBIG withdraw
							Adjuvant: MPL

¹Anti-HBsAb level ≥ 100 IU/L. HBV: Hepatitis B virus; MPL: Monophosphoryl lipid A; HBIG: Hepatitis B immunoglobulin; QS21: Quillaja saponaria Molina; HBsAb: Hepatitis B surface antibody; LT: Liver transplantation; im: Intra-muscular administration; sc: Subcutaneous administration.