Molecular epidemiology of <i>Hepatitis delta virus</i> infection in Minas Gerais state from Brazil, an area outside the hyperendemic region of the Amazon Basin

Scarponi, Cristiane FO; Kroon, Erna G; Vieira, Deusilene S; Fernandes, Ana Paula; Gomes, Karina B; Mota, Bruno EF

doi:10.1590/0074-02760190074

Abstract

BACKGROUND Hepatitis delta virus (HDV) infections in hepatitis B virus (HBV) carriers are the most severe form of viral hepatitis. HDV prevalence is high in the Brazilian Amazon, but studies in other regions of the country are still scarce and often underestimated its prevalence by including a small numbers of individuals.

OBJECTIVE This study aimed to determine the serological prevalence of hepatitis D, the genotypes circulating and to evaluate the associated risk factors for acquisition of HDV in Minas Gerais state, Brazil.

METHODS We screened plasma samples (n = 498) from HBV chronic carriers for anti-HD antibodies using a commercial enzyme-linked immunosorbent assay (ELISA) kit. For those samples that were positive for anti-HD antibodies, we performed a reverse transcriptase (RT) nested-polymerase chain reaction (nested-PCR) in order to detect the viral genome and identify the viral genotypes circulating in the state.

FINDINGS The prevalence was 6.22% (31/498). Blood transfusion was the only risk factor associated with HDV infection [risk ratio: 3.73; 95% confidence interval (CI): 1.44 to 9.65]. For 26 anti-HD positive patients, HDAg gene sequences were determined and in all patients HDV genotype 1 was found.

CONCLUSIONS This study confirmed the circulation of HDV in Minas Gerais, an area previously considered non-endemic for hepatitis D in Brazil. The prevalence found in this study is much higher when compared to other studies performed in Brazil, probably because the population in our study was selected with minimal bias. Furthermore, in 26 anti-HD positive plasma samples, we were also able to detect the viral genome, indicating that these patients were experienced an active infection at the time of sample collection. These findings emphasise the importance of anti-HD testing in HBV infected individuals, which may contribute to this disease control in Brazil.

Key words:
Hepatitis D virus genotype 1; seroprevalence; molecular epidemiology; Brazil

[TFN1] a: two-tailed p-value from Fisher’s exact test; b: two-tailed p-value from Pearson’s chi-square test; c: entered into logistic regression for multivariate analysis; d: total patients differ due to missing data.

Variable	Total anti-HD antibody		p-value
Variable	Nº negative (%)	Nº positive (%)	p-value
Age group (years)			0.068^a,c
0-19	10 (2.14)	0 (0.00)
20-39	182 (38.97)	20 (64.52)
40-59	217 (46.47)	9 (29.03)
≥ 60	58 (12.42)	2 (6.45)
Gender			0.872^b
Male	263 (56.32)	17 (54.84)
Female	204 (43.68)	14 (45.16)
Educational level^d			0.647^a
0 years	3 (1.65)	0 (0.00)
≤ 8 years	105 (57.69)	9 (69.23)
> 8 years	74 (40.66)	4 (30.77)

Variable	Total anti-HD antibody		p-value
Variable	Nº negative (%)	Nº positive (%)	p-value
IgM anti-HBc^d			0.705^a
Negative	277 (88.50)	17 (94.44)
Positive	36 (11.50)	1 (5.55)
Anti-HBe^d			0.402^a
Negative	59 (14.43)	2 (7.40)
Positive	350 (85.57 )	25 (92.59)
HBeAg^d			0.755^a
Negative	385 (88.51)	25 (92.59)
Positive	50 (11.49)	2 (7.40)
HCV/HIV coinfection			1.000^a
Negative	396 (93.84)	30 (96.77)
Positive	26 (6.16)	1 (3.23)
Chronic HBV stages^d			0.198^a,c
Inactive carrier	301 (67.33)	16 (57.14)
Active hepatitis B	85 (19.02)	6 (21.43)
Cirrhosis	32 (7.16)	5 (17.86)
Imunnotolerant	29 (6.49)	1 (3.57)
ALT levels^d			0.098^a,c
≤ UNL	351 (77.65)	19 (70.37)
> UNL, ≤ 2x UNL	88 (19.47)	5 (18.52)
> 2x UNL	13 (2.88)	3 (11.11)
Cirrhotic			0.078^b,c
No	394 (92.71)	26 (83.87)
Yes	31 (7.29)	5 (16.13)
Realised biopsy^d			0.501^a
No	385 (90.16)	27 (96.43)
Yes	42 (9.84)	1 (3.57)

Variable^d	Total anti-HD antibody		p-value
Variable^d	Nº negative (%)	Nº positive (%)	p-value
Dwelling contact with HBV carrier
No	122 (69.71)	9 (81.82)	0.317^a
Yes	53 (30.29)	2 (18.18)
Sexual contact with HBV carrier
No	112 (84.85)	6 (85.71)	0.680^a
Yes	22 (15.15)	1 (14.29)
Occupational contact with HBV carrier
No	160 (91.95)	9 (90.00)	0.582^a
Yes	14 (8.05)	1 (10.00)
Institutionalised patient
No	263 (56.32)	17 (54.84)	0.872^b
Yes	204 (46.68)	14 (45.16)
Injectable medicines
No	198 (61.49)	13 (56.52)	0.637^b
Yes	124 (38.51)	10 (43.48)
Tattoo/piercing
No	284 (87.93)	19 (82.61)	0.508^a
Yes	39 (12.07)	4 (17.39)
Accident with biological material
No	310 (93.66)	20 (86.96)	0.197^a,c
Yes	21 (6.34)	3 (13.04)
Inhaled drugs users
No	292 (90.40)	20 (86.96)	0.484^a
Yes	31 (9.60)	3 (13.04)
Acupuncture history
No	295 (94.55)	21 (87.50)	0.163^a,c
Yes	17 (5.45)	3 (12.50)
Blood transfusion
No	299 (90.06)	17 (70.83)	0.004a ^,b,c,e
Yes	33 (9.94)	7 (29.17)
Injectable illicit drugs
No	302 (93.21)	20 (86.96)	0.224^a
Yes	22 (6.79)	3 (13.04)
Surgery procedure
No	206 (64.78)	11 (50.00)	0.163^b,c
Yes	112 (35.22)	11 (50.00)
Dental procedure
No	112 (39.58)	10 (45.46)	0.588^b
Yes	171 (60.42)	12 (54.54)
Multiple sex partners
No	173 (57.67)	11 (57.89)	0.984^b
Yes	127 (42.33)	8 (42.10)
Dialysis procedure
No	313 (93.71)	21 (87.50)	0.211^a
Yes	21 (6.29)	3 (12.50)
Organ transplant
No	323 (95.56)	19 (86.36)	0.089^a,c
Yes	15 (4.44)	3 (13.64)

Molecular epidemiology of Hepatitis delta virus infection in Minas Gerais state from Brazil, an area outside the hyperendemic region of the Amazon Basin

Abstract