Prophylaxis against hepatitis B virus recurrence after liver transplantation: A registry study

Table 1 Baseline characteristics of the recipients and their donors n (%)

	Group A	Group B	Group C	P value
				A <-> B	A <-> C	B <-> C
Number of patients	4684	491	158	-	-	-
Age, mean ± SD (range) (yr)	48.2 ± 9.3 (19-76)	48.3 ± 9.5 (19-73)	48.4 ± 8 (26-71)	0.892	0.998	0.956
Male sex	4136 (88.3)	436 (88.8)	142 (89.9)	0.744	0.544	0.707
MELD score at LT, mean ± SD (range)	18.0 ± 9.5 (6-84)	17.6 ± 10.1 (6-65)	16.8 ± 9.2 (6-50)	0.205	0.250	0.847
Child-Pugh score at LT, mean ± SD (range)	8.9 ± 2.5 (5-15)	8.7 ± 2.8 (5-15)	8.7 ± 2.7 (5-14)	0.391	0.771	0.999
With HCC	2146 (45.8)	251 (51.1)	76 (48.1)	0.025	0.571	0.509
Pre-LT HBeAg positivity	1169 (25.0)	171 (34.8)	58 (36.7)	< 0.001	0.001	0.667
Pre-LT HBV DNA positivity	2248 (48.0)	168 (34.2)	62 (39.2)	< 0.001	0.030	0.251
HBV DNA ≥ 105 copies/mL at LT	1024 (21.9)	40 (8.1)	17 (10.8)	< 0.001	0.001	0.313
Pre-LT antiviral therapy	2604 (55.6)	272 (55.4)	104 (65.8)	0.934	0.011	0.021
Duration of antiviral therapy before LT, mean ± SD (range) (d)	233.4 ± 604.4 (1-7633)	92.8 ± 299.3 (1-3280)	347.1 ± 899.0 (2-7766)	0.804	< 0.001	< 0.001
Number of donors	4684	491	158	-	-	-
Age, mean ± SD (range) (yr)	28.8 ± 6.2 (18-62)	29.1 ± 6.9 (19-61)	29.3 ± 6.3 (20-51)	0.997	0.700	0.737
Male sex	4495 (96.0)	467 (95.1)	147 (93.0)	0.365	0.069	0.315
Deceased donor	4373 (93.4)	424 (86.4)	129 (81.7)	< 0.001	< 0.001	0.147
Living donor	311 (6.6)	67 (13.7)	29 (18.3)	< 0.001	< 0.001	0.147
BMI, mean ± SD (range)	22.4 ± 2.7 (15.5-52.1)	23.2 ± 2.7 (17.6-30.5)	22.6 ± 2.9 (15.8-28.4)	0.069	0.895	0.646
HBsAb positivity	606 (12.9)	68 (13.8)	27 (17.1)	0.568	0.128	0.316
HBcAb positivity	160 (3.4)	21 (4.3)	2 (1.3)	0.323	0.139	0.075

MELD: Model for end-stage liver disease; LT: Liver transplantation; HCC: Hepatocellular carcinoma; HBeAg: Hepatitis B e antigen; HBV DNA: Hepatitis B virus deoxyribonucleic acid; BMI: Body mass index; HBsAb: Hepatitis B surface antibody; HBcAb: Hepatitis B core antibody.

Table 2 Posttransplant survival of the recipients

	Group A	Group B	Group C	P value
				A <-> B	A <-> C	B <-> C
Recipients (n)	4684	491	158	--	--	--
Death during the follow-up (n)	939	57	18	--	--	--
Cumulative survival rate
1-yr	86.2%	94.4%	92.5%
3-yr	76.9%	86.6%	87.0%	< 0.001	< 0.001	0.137
5-yr	73.7%	82.4%	81.6%
Duration of follow-up, mean ± SD (range) (mo)	45.8 ± 33.7 (0-141.8)	30.2 ± 17.2 (0.1-77.1)	35.1 ± 20.5 (0.2-84.2)	--	--	--

Table 3 Posttransplant hepatitis B virus recurrence of the recipients

	Group A	Group B	Group C	P value
				A <-> B	A <-> C	B <-> C
Recipients (n)	4684	491	158	-	-	-
HBV recurrence during the follow-up (n)	179	5	3	-	-	-
Death in patients with HBV recurrence (n)	47	2	1	-	-	-
Cumulative HBV recurrence rate
1-yr	1.7%	0.5%	0.7%
3-yr	3.5%	1.5%	1.5%	0.023	0.060	0.234
5-yr	4.7%	1.5%	4.4%

Table 4 Univariate Cox proportional hazards analysis for posttransplant hepatitis B virus recurrence

Factor		Hazard ratio	95%CI	P value
Age (yr)	18-29 vs≥ 65	2.281	0.589-8.831	0.232
	30-39 vs≥ 65	1.441	0.438-4.736	0.547
	40-49 vs≥ 65	1.910	0.603-6.057	0.272
	50-64 vs≥ 65	1.657	0.522-5.262	0.392
Gender	Male vs Female	1.092	0.687-1.737	0.710
Pre-LT MELD score	6-9 vs 30-40	1.347	0.789-2.300	0.276
	10-19 vs 30-40	1.226	0.767-1.958	0.395
	20-29 vs 30-40	1.034	0.613-1.744	0.899
Pre-LT Child-Pugh score	5-6 vs 10-15	0.921	0.584-1.452	0.723
	7-9 vs 10-15	1.029	0.710-1.492	0.879
Pre-LT with HCC	Yes vs No	1.438	1.078-1.919	0.014
Pre-LT HBeAg status	Positive vs Negative	1.176	0.956-1.772	0.325
Pre-LT serum HBV DNA level
HBV DNA	Positive vs Negative	1.185	0.805-1.743	0.389
HBV DNA ≥ 105 copies/mL	Yes vs No	1.395	1.012-1.921	0.042
Pre-LT antiviral therapy
Using LAM	Yes vs No	0.930	0.697-1.241	0.622
Using ETV	Yes vs No	0.133	0.019-0.949	0.044
Using ADV	Yes vs No	0.328	0.046-2.333	0.265
Post-LT HBV prophylactic protocol	HBIG + LAM vs HBIG + ETV	2.949	1.210-7.188	0.017
	HBIG + ADV vs HBIG + ETV	1.714	0.410-7.171	0.461
Donor profiles
Donor source	Living donor vs Deceased donor	0.900	0.500-1.621	0.726
Donor gender	Male vs Female	0.564	0.298-1.067	0.078
Donor HBsAb positivity	Positive vs Negative	0.481	0.267-0.864	0.014
Donor HBcAb positivity	Positive vs Negative	1.598	0.786-3.247	0.195

LT: Liver transplantation; MELD: Model for end-stage liver disease; HCC: Hepatocellular carcinoma; HBeAg: Hepatitis B e antigen; HBV DNA: Hepatitis B virus deoxyribonucleic acid; LAM: Lamivudine; ETV: Entecavir; ADV: Adefovir dipivoxil; HBIG: Hepatitis B immunoglobulin; HBsAb: Hepatitis B surface antibody; HBcAb: Hepatitis B core antibody.

Table 5 Multivariate Cox proportional hazards analysis for posttransplant hepatitis B virus recurrence

Factor		Hazard ratio	95%CI	P value
Pre-LT with HCC	Yes vs No	1.718	1.243-2.375	0.001
Pre-LT serum HBV DNA ≥ 105 copies/mL	Yes vs No	1.370	0.989-1.897	0.048
Pre-LT using ETV	Yes vs No	0.166	0.019-1.484	0.108
Post-LT HBV prophylactic protocol	HBIG + LAM vs HBIG + ETV	2.127	0.416-3.055	0.046
Donor profiles
Donor gender	Male vs Female	0.632	0.156-1.144	0.201
Donor HBsAb positivity	Positive vs Negative	0.526	0.265-1.045	0.066

LT: Liver transplantation; HCC: Hepatocellular carcinoma; HBV DNA: Hepatitis B virus deoxyribonucleic acid; ETV: Entecavir; HBIG: Hepatitis B immunoglobulin; LAM: Lamivudine; HBsAb: Hepatitis B surface antibody.