Human herpesvirus-6 and cytomegalovirus DNA in liver donor biopsies and their correlation with HLA matches and acute cellular rejection

Guardia, Ana Carolina; Stucchi, Raquel Silveira Bello; Milan, Arlete; Costa, Sandra Cecília Botelho; Boin, Ilka de Fátima Santana Ferreira

doi:10.1016/j.bjid.2013.07.007

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Brazilian Journal of Infectious Diseases

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Brief Communications • Braz J Infect Dis 18 (02) • Mar-Apr 2014 • https://doi.org/10.1016/j.bjid.2013.07.007 copy

Human herpesvirus-6 and cytomegalovirus DNA in liver donor biopsies and their correlation with HLA matches and acute cellular rejection

Authorship SCIMAGO INSTITUTIONS RANKINGS

Herpesvirus reactivation is common after liver transplantation.

OBJECTIVE:

Analyze the presence of cytomegalovirus (HCMV) and human herpesvirus-6 (HHV-6) DNA in liver donor biopsies, seeking to better understand issues involving human donor leukocyte antigens (HLA)-A, B and DR, as well as correlations with acute cellular rejection.

METHODS:

Fifty-nine liver transplantation patients were investigated for the presence of HCMV and HHV-6 DNA in liver donor biopsies, using the Nested-PCR technique. The clinical donor information and HLA matches were obtained from the São Paulo State Transplant System. The recipients' records regarding acute cellular rejection were studied.

RESULTS:

Seven (11.8%) biopsies were positive for HCMV DNA and 29 (49%) were positive for HHV-6 DNA. In 14 donors with HLA-DR 15 nine had HHV-6 DNA positive liver biopsy with a tendency for significant association (p=0.09), 22 recipients developed acute cellular rejection and 9/22 were positive for HLA-DR 15 (p=0.03; χ ²=4.51), which was statistically significant in univariate analysis and showed a tendency after multivariate analysis (p=0.08).

CONCLUSION:

HHV-6 DNA was prevalent in liver donors studied as well as HLA-DR 15. These findings suggest that patients with HLA-DR 15 in liver donor biopsies develop more rejection after liver transplantation.

Liver transplantation; Human herpesvirus 6; Cytomegalovirus; Liver donor biopsies

Donor case	HLA			Donor liver biopsies		Post-tranplantation
	A	B	DR	HHV-6 DNA	HCMV DNA	ACR
1	2, 11	7, 27	1, 15	Positive	Positive	Positive
2	1, 2	8, 15	3, 15	Positive	Negative	Positive
3	26, 66	38, 5	11, 15	Negative	Negative	Positive
4	11, 23	44, 57	11, 15	Negative	Negative	Positive
5	2, 24	7, 57	7, 15	Positive	Positive	Positive
6	2, 3	42, 44	7, 15	Positive	Negative	Positive
7	24, 30	18, 35	11, 15	Positive	Negative	Positive
8	0, 2	40, 50	7, 15	Positive	Negative	Positive
9	24, 29	7, 44	7, 15	Negative	Negative	Positive
10	2, 11	35, 44	12, 14	Positive	Negative	Positive
11	31, 32	0, 4	4, 11	Positive	Negative	Positive
12	2, 26	15, 46	4, 13	Negative	Negative	Positive
13	1, 68	78, 55	1, 13	Negative	Negative	Positive
14	2, 32	39, 51	1, 4	Negative	Negative	Positive
15	0, 2	5, 9	4, 6	Negative	Negative	Positive
16	0, 8	2, 4	8, 1	Negative	Negative	Positive
17	2, 0	44, 39	11, 16	Negative	Negative	Positive
18	69, 35	0, 0	0, 0	Positive	Negative	Positive
19	3, 32	35, 0	8, 13	Negative	Negative	Positive
20	3, 0	15, 40	8, 11	Positive	Negative	Positive
21	2, 68	40, 57	4, 7	Negative	Negative	Positive
22	3, 11	35, 51	3, 11	Positive	Negative	Positive
23	3, 32	15, 35	1, 11	Positive	Negative	Negative
24	24, 32	35, 44	11, 15	Negative	Negative	Negative
25	3, 24	35, 44	7, 0	Negative	Negative	Negative
26	1, 3	7, 49	0, 13	Positive	Negative	Negative
27	31, 66	18, 58	12, 15	Negative	Negative	Negative
28	2, 29	15, 39	9, 13	Negative	Negative	Negative
29	1, 2	35, 51	13, 14	Positive	Negative	Negative
30	2, 31	44, 51	8, 16	Negative	Negative	Negative
31	5, 1	5, 4	8, 2	Positive	Negative	Negative
32	0, 2	44, 49	1, 7	Negative	Negative	Negative
33	11, 24	35, 37	3, 10	Negative	Negative	Negative
34	3, 1	2, 5	4, 8	Negative	Negative	Negative
35	2, 34	39, 56	1, 13	Negative	Negative	Negative
36	1, 2	18, 50	7, 11	Negative	Negative	Negative
37	24, 0	8, 51	3, 15	Positive	Negative	Negative
38	2, 3	35, 57	7, 8	Negative	Negative	Negative
39	29, 0	15, 0	10, 0	Negative	Positive	Negative
40	1, 2	8, 14	3, 7	Positive	Positive	Negative
41	3, 30	35, 53	11, 14	Positive	Negative	Negative
42	2, 30	44, 49	12, 13	Negative	Negative	Negative
43	1, 24	8, 14	1, 3	Positive	Negative	Negative
44	2, 31	15, 38	13, 16	Positive	Negative	Negative
45	26, 30	38, 58	11, 13	Negative	Negative	Negative
46	30, 68	14, 18	1, 3	Positive	Positive	Negative
47	3, 24	7, 8	13, 15	Positive	Positive	Negative
48	30, 33	14, 0	3, 15	Positive	Positive	Negative
49	2, 33	53, 0	3, 8	Negative	Negative	Negative
50	1, 30	8, 0	3, 13	Negative	Negative	Negative
51	2, 3	15, 35	3, 0	Positive	Negative	Negative
52	1, 23	15, 8	15, 0	Negative	Negative	Negative
53	2, 29	44, 50	7, 11	Negative	Negative	Negative
54	24, 0	40, 0	1, 3	Positive	Negative	Negative
55	2, 3	51, 57	1, 4	Positive	Negative	Negative
56	26, 68	27, 4	4, 13	Positive	Negative	Negative
57	11, 31	51, 56	1, 13	Positive	Negative	Negative
58	1, 2	8, 2	13, 0	Positive	Negative	Negative
59	1, 29	7, 44	1, 4	Negative	Negative	Negative

Regression summary for dependent variable: ACR R (HLA DR×ACR), R=0.39122164, R²=0.15305437, Adjusted R²=-, F(13,45)=0.62555
	b*	SE of b*	b	SE of b	t(45)	p-Value
Intercept			89.87960	34.51059	2.60441	0.012427
ICU donor	-0.026915	0.156357	-0.00393	0.02286	-0.17214	0.864100
BDC donor	0.040342	0.154217	0.01144	0.04372	0.26159	0.794831
Gender donor	0.073123	0.154645	0.07156	0.15133	0.47284	0.638611
Age donor	-0.133910	0.165004	-0.00487	0.00600	-0.81156	0.421319
BMI donor	0.089542	0.174625	0.01308	0.02551	0.51277	0.610622
Cold ischemia (min)	0.010176	0.149089	0.00002	0.00034	0.06825	0.945887
Warm ischemia (min)	-0.195094	0.163400	-0.00396	0.00331	-1.19397	0.238747
HCMV DNA donor	-0.133295	0.184690	-0.19933	0.27619	-0.72172	0.474198
HHV-6 DNA donor	-0.019943	0.156192	-0.01929	0.15108	-0.12768	0.898969
HLA DR 15 donor	0.300259	0.168916	0.33345	0.18759	1.77756	0.082234
Ender recipient	-0.075116	0.152701	-0.07774	0.15803	-0.49192	0.625171
Age recipient	0.199200	0.168171	0.00763	0.00644	1.18451	0.242431
BMI recipient	0.053993	0.156713	0.00602	0.01748	0.34453	0.732052

Brazilian Society of Infectious Diseases Rua Augusto Viana, SN, 6º., 40110-060 Salvador - Bahia - Brazil, Telefax: (55 71) 3283-8172, Fax: (55 71) 3247-2756 - Salvador - BA - Brazil
E-mail: bjid@bjid.org.br

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[1] * Corresponding author at: Rua Aldo Oliveira Barbosa 184, Campinas, SP, CEP 13086-030, Brazil. E-mail addresses: carolguardia@yahoo.com.br (A.C. Guardia), stucchi.raquel@gmail.com (R.S.B. Stucchi), arletemilan@ig.com.br (A. Milan), costa@fcm.unicamp.br (S.C.B. Costa), ilkaboin@yahoo.com, carolguardia@yahoo.com.br(I.F.S.F. Boin).