Hepatitis B and D viruses replication interference: Influence of hepatitis B genotype

Table 1 Epidemiological and clinical profiles of patients included in the transversal study n (%)

	HBV	HBV + HIV	HBV + HDV	HBV + HDV + HIV
	(n = 27)	(n = 22)	(n = 31)	(n = 37)
Age (yr)1	38.54 ± 12.22	47.33 ± 8.50	41.15 ± 9.33	42.32 ± 7.76
Gender (M/F)	21/6	12/10	22/9	17/20
Caucasian	18 (67)	20 (91)	27 (87)	33 (89)
Subsaharian	9 (33)	2 (9)	4 (13)	4 (11)
ALT (IU/mL)1	66.58 ± 76.03c	70.67 ± 18.58	112.92 ± 84.39d	90.40 ± 21.92
AST (IU/mL)1	42.65 ± 27.76	32.67 ± 19.40	89.77 ± 62.43	38.33 ± 20.12
Anti-HCV	4 (15)	2 (9)	2 (6)	3 (8)
Anti-HBe	23 (85)	17 (77)	29 (93)	31 (84)
HBeAg	4 (15)	5 (23)	2 (7)	6 (16)
HBV genotype-A	17 (63)	12 (54)	12 (42)	16 (43)
HBV genotype-D	10 (37)	10 (46)	13 (42)	20 (54)
HBV genotype-E	0	0	4 (9)	1 (3)
HBV-DNA (Log10 IU/mL)2	3.90 (3.15-5.85)e	6.97 (5.58-7.25)f	1.58 (1.00-2.43)g	2.80 (1.00-7.02)
HBsAg (Log10 IU/mL)2	4.00 (3.81-4.22)h	5.46 (4.15-5.61)i	3.83 (3.59-4.39)j	3.83 (3.24-4.38)k
HDV-RNA (Log10 copies/mL)2	NA	NA	5.20 (4.37-5.74)	6.89 (4.41-7.73)

¹Data expressed as Mean ± SD;

²Data expressed as Median (IQR); c vs d: P = 0.043; e vs f: P = 0.007; f vs g: P = 0.037; h vs i: P = 0.001; j vs i and i vs k: P < 0.001. HBV genotypes data reported in this table has been obtained by commercial LIPA assay or using, in the negative cases, the PCR/sequencing method developed in this work. In two patients with CHD/HIV negative, the HBV genotype was not determined. HDV genotype 1 was found in the 60 Caucasian patients and in 6/8 (75%) of the immigrant Subsaharian patients. In the remaining 2 patients, HDV genotypes 3 and 4 were respectively detected, one of them infected with HBV-A and the other with HBV-D. In only 25 (37%) patients data about HBV/HDV coinfection date were available. No differences in the HBV duration of infection were observed between patients infected with HBV-A or HBV-D (mean ± SD: 21.5 ± 5.3 vs 23.75 ± 6.2 yr, respectively). HBV: Hepatitis B virus; HDV: Hepatitis delta virus; HIV: Human immunodeficiency virus; CHD: Chronic hepatitis delta; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase.

Table 2 Epidemiological and clinical profiles of patients

	Age1	Gender	Precedence	Mode of	Duration of	HBV Genotype2	Previous	Time without Treatment3 (mo)	Follow-up (mo)	Sampling
				transmission	infection (yr)		treatment
Pat #1	43	Male	Western Europe	Horizontal	20	Undetermined	IFN	84	74	8
Pat #2	30	Male	Equatorial Ginnea	Unknown	Unknown	A	No		5	4
Pat #3	41	Male	Equatorial Ginnea	Unknown	Unknown	E	No		2	3
Pat #4	43	Male	Eastern Europe	Unknown	Unknown	A	No		5	3
Pat #5	45	Male	Western Europe	IVD	Unknown	A	No		4	4
Pat #6	38	Female	Western Europe	Horizontal	20	D	IFN	36	94	10
Pat #7	35	Female	Western Europe	Horizontal	25	E	IFN	60	89	13
Pat #8	55	Female	Western Europe	Unknown	Unknown	D	No		17	3
Pat #9	37	Male	Equatorial Ginnea	IVD	22	A	IFN/ADV	8	77	12
Pat #10	31	Female	Western Europe	Horizontal	20	D	IFN	12	78	12
Pat #11	46	Male	Western Europe	IVD	25	A	No		53	4
Pat #12	42	Male	Western Europe	Unknown	26	D	No		93	13
Pat #13	45	Male	Western Europe	Unknown	Unknown	A	No		42	3
Pat #14	39	Male	Western Europe	IVD	20	D	No		41	6
Pat #15	53	Male	Western Europe	IVD	25	D	No		89	14
Pat #16	38	Female	Equatorial Ginnea	Unknown	Unknown	E	No		9	5

¹Data of age are referred to the first sample analyzed of each patient;

²HBV genotype data correspond to the LiPA/PCR-sequencing assays;

³Time interval between the end of the previous treatment and the sampling of the first sera included in this study. No statistical differences in the route of infection, duration of infection, or previous antiviral treatment were found between patients infected with the different HBV genotypes. HBV: Hepatitis B virus; IFN: Interferon; ADV: Adefovir; IVD: Intra venous drug user.

Table 3 Hepatitis B virus serological profile of patients

			Serum HBV-DNA			HBsAg
	Genotype1	Anti-HBe	Status2	Log10 (IU/mL) (range)	VC	Log10 (IU/mL) (range)	VC
Pat #1	Und	Positive	Negative	NA	NA	4.40 ± 0.13 (4.20-4.48)	0.03
Pat #2	A	Positive	Negative	NA	NA	4.60 ± 0.09 (4.56-4.66)	0.02
Pat #3	E	Positive	Positive	2.80 ± 0.29 (2.60-3.01)	0.10	4.46 ± 0.10 (4.39-4.53)	0.02
Pat #4	A	Positive	Positive	1.75 ± 1.20 (1.30-2.95)	0.69	3.53 ± 0.14 (3.44-3.63)	0.04
Pat #5	A	Positive	Positive	3.25 ± 1.30 (2.13-4.35)	0.40	4.87 ± 0.06 (4.86-4.93)	0.01
Pat #6	D	Positive	Fluctuating	2.32 ± 0.70 (1.00-3.42)	0.30	4.52 ± 0.27 (4.01-4.78)	0.06
Pat #7	E	Positive	Fluctuating	1.36 ± 0.45 (1.00-2.48)	0.33	3.94 ± 0.10 (3.80-4.12)	0.03
Pat #8	D	Positive	Fluctuating	1.65 ± 0.92 (1.00-2.30)	0.56	4.64 ± 0.07 (4.59-4.69)	0.02
Pat #9	A	Positive	Fluctuating	1.62 ± 0.88 (1.00-2.48)	0.54	4.17 ± 0.68 (3.68-4.64)	0.16
Pat #10	D	Positive	Positive	3.17 ± 0.56 (2.22-4.08)	0.18	3.99 ± 0.19 (3.64-4.13)	0.05
Pat #11	A	Positive	Negative	NA	NA	4.55 ± 0.07 (4.48-4.63)	0.02
Pat #12	D	Negative	Fluctuating	3.22 ± 1.40 (1.00-4.99)	0.43	4.45 ± 0.09 (4.30-4.58)	0.02
Pat #13	A	Positive	Negative	NA	NA	3.85 ± 0.17 (3.73-3.97)	0.04
Pat #14	D	Positive	Fluctuating	2.11 ± 0.73 (1.00-2.93)	0.35	3.75 ± 0.10 (3.68-3.82)	0.03
Pat #15	D	Positive	Positive	2.76 ± 0.95 (1.97-4.76)	0.34	3.55 ± 0.20 (3.20-3.73)	0.06
Pat #16	E	Positive	Positive	2.36 ± 0.10 (2.30-2.48)	0.04	4.28 ± 0.10 (4.21-4.35)	0.02

¹Genotyping results obtained by the combined use of LiPA and PCR/Sequencing techniques (see material and methods);

²Evolution of HBV-DNA during follow-up. Fluctuating is defined as a patient with alternating positive and negative samples. HBV: Hepatitis B virus; VC: Variation coefficient; NA: Not applicable; Und: Undetermined genotype because of HBV-DNA negativity.

Table 4 Hepatitis delta virus serological profiles of patients

	HDV markers					HCV markers
			Serum HDV-RNA			Serum HCV-RNA
	Genotype	Anti-HD IgM	Status1	Log10 (copies/mL) (range)	VC	Anti-HCV	HCV-RNA
Pat #1	Und	Negative	Positive	5.90 ± 0.31 (5.53-6.11)	0.05	Negative	NA
Pat #2	A	Negative	Positive	5.69 ± 0.05 (5.64-5.72)	0.01	Negative	NA
Pat #3	E	Negative	Positive	5.11 ± 0.12 (5.02-5.20)	0.02	Negative	NA
Pat #4	A	Negative	Positive	4.38 ± 1.64 (2.60-5.84)	0.37	Negative	NA
Pat #5	A	Negative	Positive	6.47 ± 0.64 (5.70-7.18)	0.10	Negative	NA
Pat #6	D	Positive	Positive	4.55 ± 2.26 (1.08-5.75)	0.50	Negative	NA
Pat #7	E	Positive	Positive	4.01 ± 0.31 (3.57-4.43)	0.08	Negative	NA
Pat #8	D	Positive	Positive	4.13 ± 0.35 (3.89-4.38)	0.08	Negative	NA
Pat #9	A	Positive	Fluctuating	2.14 ± 0.99 (1.00-3.31)	0.46	Negative	NA
Pat #10	D	Positive	Fluctuating	4.07 ± 1.72 (1.00-5.07)	0.42	Negative	NA
Pat #11	A	Negative	Positive	5.47 ± 1.33 (4.53-5.47)	0.24	Negative	NA
Pat #12	D	Positive	Positive	4.76 ± 1.46 (1.70-6.22)	0.31	Negative	NA
Pat #13	A	Positive	Positive	4.53 ± 0.16 (4.41-4.64)	0.04	Negative	NA
Pat #14	D	Negative	Fluctuating	3.08 ± 2.95 (1.00-5.17)	0.96	Positive	Negative
Pat #15	D	Negative	Negative	NA	NA	Positive	Negative
Pat #16	E	Positive	Positive	6.26 ± 0.74 (5.74-6.78)	0.12	Negative	NA

¹Evolution of HDV-RNA during follow-up. Fluctuating is defined as a patient with alternating positive and negative samples. HDV genotype was I in the 16 samples analyzed. The number of patients with HCV infection was too low to perform statistical analysis. Und: undetermined genotype due to HBV-DNA negativity. VC: Variation coefficient; NA: Not applicable; HBV: Hepatitis B virus; HCV: Hepatitis C virus; HDV: Hepatitis delta virus.