Basal core promoter and precore mutations among hepatitis B virus circulating in Brazil and its association with severe forms of hepatic diseases

Chachá, Silvana Gama Florencio; Gomes-Gouvêa, Michele Soares; Malta, Fernanda de Mello; Ferreira, Sandro da Costa; Villanova, Márcia Guimarães; Souza, Fernanda Fernandes; Teixeira, Andreza Correa; Passos, Afonso Dinis da Costa; Pinho, João Renato Rebello; Martinelli, Ana de Lourdes Candolo

doi:10.1590/0074-02760160540

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ARTICLES • Mem. Inst. Oswaldo Cruz 112 (9) • Sept 2017 • https://doi.org/10.1590/0074-02760160540 copy

Basal core promoter and precore mutations among hepatitis B virus circulating in Brazil and its association with severe forms of hepatic diseases

Authorship SCIMAGO INSTITUTIONS RANKINGS

BACKGROUND

In Brazil, few studies have investigated the prevalence of infection with the precore (PC) and basal core promoter (BCP) mutants of the hepatitis B virus (HBV).

OBJECTIVES

This study aimed to analyse the frequency of PC and BCP mutations among patients infected with HBV and to evaluate the association between the variants and advanced hepatic disease.

METHODS

A total of 161 patients infected with HBV were studied. To identify PC and BCP mutations, a 501-bp fragment of HBV DNA was amplified and sequenced.

FINDINGS

PC and BCP regions from HBV strains were successfully amplified and sequenced in 129 and 118 cases, respectively. PC and BCP mutations were detected in 61.0% and 80.6% of the cases, respectively. The A1762T/G1764A variant was identified in 36.7% of the patients with grade 1 and 2 liver fibrosis (29/79) and in 81.8% of the patients with grade 3 and 4 liver fibrosis (9/11) (p < 0.01); in 76.9% of the patients with cirrhosis (10/13) and in 38.1% of the patients without cirrhosis (40/105) (p = 0.01); and in 77.8% of the patients with hepatocellular carcinoma (HCC) (7/9) and in 39.4% of the patients without HCC (43/109) (p = 0.03).

MAIN CONCLUSIONS

A high prevalence of HBV PC and BCP mutants was found. The A1762T/G1764A variant was independently associated with advanced forms of liver fibrosis, hepatic cirrhosis, and HCC.

hepatitis B virus; basal core promoter mutant; precore mutant; Brazil

	HBeAg positive n = 26	HBeAg negative chronic hepatitis n = 108	Inactive carrier n = 27	p
Age (years)
mean	39.9	45.0	44.4	0.16^a
standard deviation	13.1	11.9	11.8
median	40.5	44.0	41.0
range	21-76	19 - 77	24 - 70
male	21 (80.7%)	72 (66.7%)	11 (40.7%)	< 0.01^b,c
female	5 (19.2%)	36 (33.3%)	16 (59.3%)
Alcohol abuse	5 (19.2%)	11 (10.2%)	1 (3.7%)	0.18^b
Cirrhosis	5 (19.2%)	19 (17.6%)	-	0.54^b
HCC	1 (3.8%)	13 (12.0%)	-	0.47^b
Liver fibrosis	n = 21	n = 97	n = 7
1 or 2	19 (90.5%)	77 (79.4%)	7 (100.0%)	0.35^b
3 or 4	2 (9.5%)	20 (20.6%)	-

BCP mutations n = 118	Evolutionary phase of HBV infection						p

	HBeAg+ chronic hepatitis n = 19		HBeAg-chronic hepatitis n = 76		Inactive carrier n = 23
	n	%	n	%	n	%
A1762T/G1764A	4	15.4	17	15.7	1	3.7	0.03^a
T1753C (G or A)/ A1762T/G1764A	3	11.5	22	20.5	4	14.8
Other BCP variants	2	7.7	17	15.7	-	-
No BCP mutations	10	38.5	20	18.5	18	66.7	< 0.01^b

Total	19	100	76	100	23	100

PC mutations n = 129	Evolutionary phase of HBV infection						p

	HBeAg+chronic hepatitis n = 20		HBeAg-chronic hepatitis n = 85		Inactive carrier n = 24

	n	%	n	%	n	%
G1862T	7	35.0	16	18.8	5	20.8	0.28
G1896A	2	10.0	20	23.5	11	45.8	0.03^c
G1896A/G1899A	1	5.0	19	22.4	-	-
Other PC mutations	-	-	18	21.2	-	-
No PC mutations	10	50.0	12	14.1	8	33.4	< 0.01^d

Total	20	100	85	100	24	100

	With cirrhosis n = 24	Without cirrhosis n = 137	p	With HCC n = 14	Without HCC n = 147	p	Total N = 161
BCP mutations^a n =118
A1762T/G1764A	10 (76.9%)	40 (38.1%)	0.01	7 (77.8%)	43 (39.4%)	0.03	50 (42.4%)
PC mutations^b n = 129
G1862T	8 (50.0%)	31 (27.4%)	0.08	5 (45.4%)	34 (28.8%)	0.30	39 (30.2%)
G1896A	6 (37.5%)	50 (44.2%)	0.78	5 (45.4%)	51 (43.2%)	1.00	56 (43.4%)
G1862T/G1896A	-	1 (0.9%)	-	-	1 (0.8%)	-	1 (0.8%)

	With cirrhosis n = 24	Without cirrhosis n = 137	p	With HCC n = 14	Without HCC n = 147	p	Total N = 161
Gender			0.04			0.38
male	20 (83.3%)	84 (61.3%)		11 (78.6%)	93 (63.3%)		104 (64.6%)
female	4 (16.7%)	53 (38.7%)		3 (21.4%)	54 (36.7%)		57 (35.4%)
Age (mean in years)	55.5	42.1	< 0.01	54.5	43.1	< 0.01	44.1
Alcohol abuse	4 (16.7%)	13 (9.5%)	0.28	3 (21.4%)	14 (9.5%)	0.17	17 (10.6%)

Instituto Oswaldo Cruz, Ministério da Saúde Av. Brasil, 4365 - Pavilhão Mourisco, Manguinhos, 21040-900 Rio de Janeiro RJ Brazil, Tel.: (55 21) 2562-1222, Fax: (55 21) 2562 1220 - Rio de Janeiro - RJ - Brazil
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[1] + Corresponding author: sgfchacha@gmail.com