A novel stop codon mutation in HBsAg gene identified in a hepatitis B virus strain associated with cryptogenic cirrhosis

Table 1 Viral and clinical examination results of the patient

Item	Jan.1999	Apr.1999	Oct.1999	Aug. 2000	Nov. 2000	Mar. 2001
HBsAg	-	-	-	-	-	-
Anti-HBs	+	+	+	+	+	+
HbeAg	+		+	+	+	+
Anti-Hbe	-	-	-	-	-	-
Anti-HBc-IgG	+	+	+	+	+	+
Anti-HBc-IgM	+	-	-	-	-	-
HBV DNA	Nd	Nd	Nd	Nd	+	+
HBV DNA copies/ml	Nd	Nd	Nd	Nd	1.02 × 108	1.54 × 109
ALT (U/L)	49.0	56.9	67.1	74.4	69.0	68.6
Albumin (g/L)	42.3	40.4	38.5	40.3	41.5	40.8
Globulin (g/L)	28.6	30.7	28.5	34.4	31.9	32.6
Bilirubin (μmol/L)	18.9	23.2	28.6	25.8	27.7	28.4
Hemoglobin (g/L)	Nd	Nd	Nd	111	115	110
WBC (109/L)	Nd	Nd	Nd	2.1	2.8	2.6
Platelet (109/L)	Nd	Nd	Nd	26	58	40

Nd, not determiined; +, positive; -, negative. ALT, alanine aminotransferase; WBC, white blood cell.

Table 2 HBsAg, HBeAg and anti-HBc level determined using Abbott reagent

Item	Results	Cut off
HBsAg	0.77	≥ 2.00(S/N)
HbeAg	56.433	≥ 2.10(S/N)
Anti-HBc	2.033	≤ 1.0(S/Co)

Table 3 The complete nucleotide sequence of the HBsAg gene from the patient

nt																Codon
155	ATG	GAG	AAC	ATC	ACA	TCA	GGA	TTC	CCA	GGA	CCC	CTG	CTC	GTA	TTA	15
200	CAG	GCG	GGG	TTT	TTC	TTG	TTG	ACA	AAA	ATC	CTC	ACA	ATA	CCA	CAG	3 0
245	AGT	CTA	GAC	TCG	TGG	TGG	ACT	TCT	CTC	AAT	TTT	CTA	GGG	GGA	ACA	45
290	CCC	GTG	TGT	CTT	GGC	CAA	AAT	TCG	CAG	TCC	CAA	ATC	TCC	AGT	CAC	60
335	TAA	CCA	ACC	TGC	TGT	CCT	CCA	ATT	TGT	CCT	GGT	TAT	CGC	TGG	ATG	75
380	TGT	CTG	CGG	CGT	TTT	ATC	ATC	TGC	CTC	TGC	ATC	CTG	CTG	CTA	TGC	90
425	CTC	ATC	TTC	TTG	TTG	GTT	CTT	CTG	GAC	TAT	CAA	GGT	ATG	TTG	CCC	105
470	GTT	TGT	CCT	CTA	CTT	CCA	GGA	TCA	ACA	ACA	ACC	AGC	ACC	GGA	CCA	120
515	TGC	AAA	ACC	TGC	ACG	ACT	CCT	GCT	CAA	GGC	AAC	TCT	AAG	TTT	CCC	135
560	TCT	TGT	TGC	TGT	ACA	AAA	CCT	ACG	GAC	GGA	AAC	TGC	ACC	TGT	ATT	150
605	CCC	ATC	CCA	TCA	TCT	TGG	GCT	TTC	GCA	AAA	TAC	CTA	TGG	GAG	TGG	165
650	GCC	TCA	GTC	CGT	TTC	TCT	TGG	CTC	AGT	TTA	CTA	GTG	CCA	TTT	GTT	180
695	CAG	TGG	TTC	GTA	GGG	CTT	TCC	CCC	ACT	GTC	TGG	CTT	TCA	GTT	ATA	195
740	TGG	ATG	ATG	TGG	TTT	TGG	GGG	CCA	AGT	CTG	TAC	AAC	ATC	GTG	AGT	210
785	CCC	TTT	ATG	CCG	CTG	TTA	CCA	ATT	TTC	TTT	TGT	CTC	TGG	GTA	TAC	225
830	ATT	TAA														227

Table 4 Comparison of nucleotide sequences and amino acid sequences of HBsAg gene among the 3 adw subtypes

Codon	4	9	14	24	29	45	47
Sequence(1)	ATC Ile	CTA Leu	GTG Val	AGA Arg	CCG pro	TCA Ser	CTA Leu
Sequence(2)	ATC Ile	CCA Pro	GTA Val	AAA Lys	CCA Pro	TCA Ser	GTA Val
Sequence(3)	ACA Thr	CTA Leu	GTG Val	AGA Arg	CCA Pro	GCT Ala	GTA Val
Codon	49	56	57	59	61	64	71
Sequence(1)	CCT pro	CCA His	ACC Thr	AAT Asn	TCA Ser	TCC Ser	GGT Gly
Sequence(2)	CTT Leu	CAA Glu	ATC Ile	AGT Ser	TAA stop	TGT Cys	GGT Gly
Sequence(3)	CTT Leu	CCA His	ACC Thr	AAT Asn	TCA Ser	TCT Ser	GGC Gly
Codon	82	83	85	94	99	100	110
Sequence(1)	ATA Ile	TTC Phe	TTC Phe	TTA Leu	GAT Asp	TAT Tyr	ATT Ile
Sequence(2)	ATC Ile	TGC Cys	TGC Cys	TTG Leu	GAC Asp	TAT tyr	CTT Leu
Sequence(3)	ATA Ile	TTC Phe	TTC Phe	TTG Leu	GAC Asp	TAC Tyr	CTT Leu
Codon	113	114	115	117	118	122	126
Sequence(1)	TCA Ser	ACA Thr	ACA Thr	AGT Ser	ACG Thr	AAA Lys	ACT Thr
Sequence(2)	TCA ser	TCA Ser	ACA Thr	AGC Ser	ACC Thr	AAC Lys	ACT Thr
Sequence(3)	ACA Thr	TCA Ser	ACT Thr	AGC Ser	ACG Thr	AAG Lys	ATT Ile
Codon	130	131	132	136	143	144	146
Sequence(1)	GGC Gly	AAC Asn	AAG Lys	TCA Ser	ACG Thr	GAT Asp	AAT Asn
Sequence(2)	GGA gly	ACC Thr	ATG Met	TCA Ser	ACG Thr	GAC Asp	AAC Asn
Sequence(3)	GGA Gly	ACC Thr	ATG Met	TCT Ser	TCG Ser	GAC Asp	AAC Asn
Codon	148	154	155	160	161	171	190
Sequence(1)	ACC Thr	TCG Ser	TCC Ser	AAA Lys	TAC Thr	TCT Ser	GTT Val
Sequence(2)	ACC Thr	TCA Ser	TCT Ser	AAA Lys	TAC Thr	TCT Ser	GTC Val
Sequence(3)	ACT Thr	TCA Ser	TCT Ser	AGA Agr	TTC Phe	TCC ser	GTT val
Codon	194	200	207	209	213	214	215
Sequence(1)	GCT Ala	TAT Thr	AGC Ser	GTG Val	ATA Ile	CCG Pro	CTC Leu
Sequence(2)	GTT Val	TTT Phe	AAC Asn	TTG Leu	ATG met	CCG Pro	CTG Leu
Sequence(3)	GTT val	TAT Thr	AAC Asn	TTG Leu	TTA Leu	CCT Pro	CTA Leu
Codon	222
Sequence(1)	CTC Leu
Sequence(2)	CTC Leu
Sequence(3)	CTT Leu

Sequence (1): adw subtype reported by Ono et al[9]. Sequence (2): The patient’s sequence. Sequence (3): The Chinese consensus sequence of adw subtype.