Genotypes and viral variants in chronic hepatitis B: A review of epidemiology and clinical relevance

Table 1 Geographic distribution of genotypes by continent

	Region	Genotype distribution
Africa	Subsaharan Africa (Egypt, Algeria, Libya)	Genotype D
	West Africa (Guinea Bissau, Ghana, Cameroon)	Genotype E and also A
	Central Africa	Genotype E and also A
	East Africa (Malawi, Tanzania)	Genotype A
	South Africa	Genotype A
Europe	Mediterranean Basin (Greece, Italy, Spain)	Genotype D in majority. Gentype A also seen in Spain
	Western Europe	Mixtures of A-D from various migrant groups
	Eastern Europe	A (Czech republic, Poland) and D (Russia, Croatia, Romania)
Americas	North America	Mixtures of A-D from various migrant populations Genotype F and B in Alaskan natives
	Central America	Genotype H (Mexico) Genotype F (Costa Rica)
	South America	Genotype F predominant and Genotypes A and D in Brazil/Argentina
Asia	Western Asia ( Iran, Yemen, Saudi Arabia, Turkey)	Genotype D
	Central Asia (Uzbekistan, Tajikistan, Afghanistan, Pakistan)	Genotype D
	South Asia (India and Pakistan)	Genotype D in India but also Gentoype A

Table 2 Prevalence of different hepatitis B virus genotypes in Southeast Asian countries and China

	No. instudy	Genotypedistribution	Notes	Ref.
Laos	386	42.2% B 55.4% C 2.4% not typable ? I	Cohort of patients from Vientiane city and central provinces. 19 patients did not group into genotype A-H ? genotype I	[55]
Cambodia	12	67% C , 33% B (subtype 4)		[56]
	22	72% C 28% B		[57]
Vietnam	76	51% B, 48.7% C	Chronic cohort	[58]
	40	75% B 18% C 2.5% B + C, 5% not determined	Based in Hanoi	[59]
Indonesia	54	76% B		[60]
		24% C
	54	100% B	Surabaya	[61]
	27	85% C 7.4% B 7.4% D	Papua	[62]
Malaysia	86	60% B	Genotype B 80% in ethnic Chinese	[63]
		34% C	Genotypes B and C equal prevalence in Ethnic Malays
		2% D	Gentoype D in Indian patients
	51	56.9% B 31.4% C 7.8% B + C 2% each D and E		[64]
Thailand	224	86.6% C (Subgeno C1) 11.2% B 0.44% each of A and D 3 suspected recombinations	Myanmar ethnicity 97.5% genotype C Laos ethnicity 71% C 26% B, Cambodia 84% C, 12% B	[65]
	216	89.3% C 7.4% B, 1.9% B + C, 0.5% A	Northern Thailand adult voluntary blood donors	[66]
	53	90.6% C 7.5% B 1.9% B + C	Children in Chiang Mai	[67]
	332	73.2% C 20.8% B 3.3% A 2.7% unclassified	Cohort included CHB and HCC patients and found that genotype B was not associated with HCC in younger patients	[68]
Philippines	100	51% A 22% B 27% C		[69]
	50	28% A 12% B 26% C 6% Mixed A + C/A + B + C 28% Non typable		[70]
China	101	36% B 64% C	Hong Kong 42% B Shnaghai 39% B Beijing 20% B	[71]
	121	33% B 63.6% C 1.7% B/C 1.7% D	From Beijing China	[72]
	126	38.1% B 54.8% C 0.8% D, 3.2% unknown 1.6% B/C, 1.6% A/C	Yunnan China	[73]
	142	9.2% B 88% C 2.8% D	Northern China (Harbin University China)	[74]
	142	4.2% A 14.1% B 78.9% C 1.4% D	Southern China (Nanning)	[75]
	786	63.23% B 34.99% C 0.89% A and D each	Southern China (Guizhou )	[76]
	220	1.4% A 17.2% B 81.4% C	Shanghai China	[77]
China (Hong Kong)	776	1.5% A 32.5% B 62.6% C 3.4% Mixed	Hong Kong	[78]
Tibet	26	96% C/D recombinant 4% C	Sequences based on surface Ag gene showed that 25 clustered with genotype D and 1 clustered with genotype C. However based on core gene all clustered with genotype C	[79] .

Table 3 Clinical associations with hepatitis B virus genotypes

	A	B	C	D	E	F
Progression to chronicity	+++	++	+++	++
Histological inflammation	++	++	+++	+++		+/-
Histological fibrosis	+	+	++	++		+/-
Association with advanced liver disease	+	++	+++	++		+/-
Association with HCC	+ (subgeno A1)	+	++	++		++ (subgeno F2)
Early HBeAg seroconversion	++	+++	+	+++		+++
Sustained remission after HBeAg Seroconversion	+++	+++	++	++		++
HBsAg clearance	+++	++	+	++
Response to IFN Tx	+++	++	+	+/-	+	+++
Association with PreCore mutations	-	++	+	+++	++	+++ (F1 but not F2)
Association with BCP mutation	++		++		++

+/-: Possible association; - : No association; +: Slight association; ++: Moderate association; +++: Strong association. HBeAg: Hepatitis B e antigen; BCP; Basal core promotor; HCC: Hepatocellular carcinoma; IFN: Interferon.