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Copyright ©The Author(s) 2016.
World J Gastroenterol. Jan 7, 2016; 22(1): 165-175
Published online Jan 7, 2016. doi: 10.3748/wjg.v22.i1.165
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 protocolHBV recurrence
Angus et al[34], 20003218.432 LAM (100 mg/d)400 IU or 800 IU/d im for 1 wk and then 400 IU or 800 IU/mo1/32 (3.1%) HBsAg+
0/32 (0%) HBV-DNA+
Gane et al[35],200714762147 LAM (100 mg/d)400 IU or 800 IU/d im for 1 wk and then 400 IU or 800 IU/mo5/147 (3.4%)
actuarial risk of HBV recurrence was 1% at 1 yr and 4% at 5 yr
Karademir et al[36], 2006351633 LAM6000 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, thereafter2/35 (5.7%)
2 LAM + ADVTwo HBV recurrent case had LAM resistance at LT
Iacob et al[38], 20084221.642 LAM10000 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, thereafter2/48 (4.8%)
Jiang et al[37], 201025441.2254 LAM2000 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, thereafter14/254 (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et al[41], 20061414.114 LAM + ADV10000 IU HBIG iv in anhepatic phase and 10000 IU/d for first 1 wk, and then HBIG was withdrawn and replaced with oral ADV1/14 (7.1%)
HBV recurrent case showed normal liver function.
Angus et al[42], 2008342118 LAM + HBIGRandomized trial0/18 in HBIG + LMV
16 LAM to LAM + ADVAll patients were treated with low-dose im HBIG + LMV ≥ 1 yr post-LT1/16 (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], 2011611519 LAM to LAM + ADVAll 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 left2/61 (3.3%)
41 LAM to LAM + TFVBoth recurrent case was HBsAg+/HBV-DNA- without liver dysfunction
1 ETV to ETV + ADV
Table 2 Main results of published studies using vaccination after liver transplantation
Ref.Patients (n)Age, median (yr)HBV-DNA negative before LTDuration between LT and vaccinationMomo immunosuppressionResponse to vaccination1Vaccination protocol(dose:μg)
Sánchez-Fueyo et al[59], 20002239100%33%63.522.7%40 im/40 im
3 + 3 (/cycle)
without HBIG
Angelico et al[60], 20021753100%48%10011.8%40 im/10 sc/40 im
3 + 6 + 3 (/cycle)
without HBIG
Bienzle et al[63], 20032054100%78%8080%20 im or 100 im
5 + 3 (/cycle)
with HBIG Adjuvant: MPL + QS21
Stärkel et al[64], 2005104990%55%10040%40 im/40 im
5 (/cycle)
with HBIG
Adjuvant: MPL
Lo et al[66], 2005524781%14%92.31.9%40 im
3 + 3 (/cycle)
without HBIG
Rosenau et al[62], 200685037.5%60%37.512.5%20 im
6 (/cycle)
without HBIG
Lo et al[66], 2007205280%21%8535%HBs + preS 20 im
3 + 3 (/cycle)
without HBIG
Tahara et al[69], 2009205375%20%6065%20 im or 40 im
unrestraint
with HBIG
under immune-monitoring
Di Paolo et al[65], 20101859100%73%8944%20 im
6 + 6 (/cycle)
HBIG withdraw
Adjuvant: MPL