Clinical relevance and public health significance of hepatitis B virus genomic variations

Table 1 Geographic distribution and important clinical relevance of HBV genotypes and subgenotypes

Genotype	Subgenotype	Geographic distribution	Important clinical relevance	Ref.
A	A1	Africa	ND	[13-15]
	A2	Europe	Acute infection, chronicificaton, more sensitive to interferon treatment than genotype D	[11,12,47,48]
	A3	West Africa	ND	[13-15]
	A4	West Africa	ND	[15]
	A5	West Africa	ND	[14,15]
B	B1	Japan	Fulminant hepatitis	[16]
	B2	Most of Asia, except Korea	Acute hepatitis, HCC in mostly those younger than 50 years	[6,10]
	B3	Indonesia	ND	[17,18]
	B4	Indonesia, Vietnam	ND	[18,19]
	B5	Indonesia, Philippines	ND	[17,18,22]
	B6	Indonesia	ND	[28]
	B7	Indonesia	ND	[17,18]
	B8	Indonesia	ND	[17]
C	C1	South Asia, Southern China	HCC and LC	[18]
	C2	Northeast Asia, China	HCC and LC mostly in those older than 50 years	[6,10]
	C3	Indonesia, Oceania	ND	[18,19]
	C4	Australia	ND	[19]
	C5	Indonesia, Philippines	ND	[17,22]
	C6	Indonesia, Philippines	ND	[17,21]
	C7	Indonesia	ND	[17]
	C8	Philippines	ND	[20,21]
	C9	Tibet, China	ND	Unpublished
D	D1 (mainly D)	Middle East, the Mediterranean area	Chronic liver disease, HCC	[13,23-25,37,81]
	D2	Russia, the Baltic region, India	No apparent clinical relevance	[26,32]
	D3	Indonesia, India	Occult HBV infection	[17,32]
	D4	Oceania	ND	[19]
	D5	India	No apparent clinical relevance	[32]
	D6	Indonesia	ND	[33]
	D7	Tunisia	ND	[34]
E	ND	Western and Central Africa	ND	[13,27,35]
F	F Ia	Central America	HCC	[29,36,62]
		Chile, Alaska
	F Ib	Argentina, Japan, Venezuela, USA
	F II	Brazil, Venezuela, Nicaragua
	F III	Venezuela, Panama, Columbia
	F IV	Argentina, Bolivia, France
G	ND	Mexico, Canada	ND	[30,31]
H	ND	Mexico	ND	[30]
I	ND	Vietnam, Laos	ND	[7,8]
J	ND	Japan (might be from Borneo)	HCC	[9]

HBV: Hepatitis B virus; ND: Not determined; HCC: Hepatocellular carcinoma.

Table 2 HBV mutations associated with drug resistance

Nucleoside analogs	Mutations in the polymerase domains (amino acids)
	A	B	C (YMDD)	D	E
Lamivudine/	-	V173L	M204I/V	-	-
Emtricitabine		L180M
Adefovir	-	A181V	I233V	N236T	-
Entecavir	-	I169T	S202I	M250V	-
		T184G
Telbivudine	-	-	M204I	-	-
Famciclovir	-	L180M	-	-	-

-: Not reported.