Mapping Hepatitis B Virus Genotypes, Recombinant Genotypes and Sub- genotypes on the African continent from 1997 to 2021: A Systematic Review with Meta-Analysis

doi:10.21203/rs.3.rs-1998327/v1

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Mapping Hepatitis B Virus Genotypes, Recombinant Genotypes and Sub- genotypes on the African continent from 1997 to 2021: A Systematic Review with Meta-Analysis

https://doi.org/10.21203/rs.3.rs-1998327/v1

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published 07 Apr, 2023

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Hepatitis B virus (HBV) has ten genotypes (A-J) based on the divergence of ≥ 8% in the complete genome. These genotype influence disease prognosis, response to therapy and route of viral transmission. This study aimed at mapping the de novo genotype, sub-genotypes as well as genotype mixtures and correlate them with the immigration trends in order to inform future research about the relative distribution of HBV genotypes from a large sample size.

A total of 60 full research articles obtained from reputable electronic data bases which included Scopus, PubMed, EMBASE, Willy library, African Journal Online (AJOL) and Google Scholar were analysed for data extraction between February 10th and March 28th 2022. The prevalence of the genotypes, sub-genotypes, recombinant genotypes and I² statistics for heterogeneity were calculated using MedCalc software version 20.010. The Z-test was used to compare the the relative proportions of the various genotypes by region. The Chi-square test was used for the analysis of the relative prevalence of the emerging genotypes B and C on the African continent by region. In contrast, Fisher’s exact test was used in the analysis of the prevalence of sub-genotypes and genotype mixtures by country. Finally, meta-regression analysis was used for the analysis of the variations in the prevalence of dominant genotype, other genotypes and sub-genotypes/recombinant genotypes over the past 25 years on the continent. Sources of heterogeneity were analysed through meta-regression, and sub-group analysis at 95% CI. A P < 0.05 was considered significant for all analyses. The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO), University of York Centre for Reviews and Dissemination (https://www.crd.york.ac.uk/PROSPERO), under the registration number CRD42022300220

Overall, genotype E had the highest pooled prevalence significantly higher than all the other genotypes (p < 0.001). By region, genotype A posted the highest pooled prevalence in eastern and southern, E in west Africa and D in north Africa (p < 0.0001). Additionally, genotype B was significantly higher in south Africa and C in east Africa (p < 0.0001). A1 and B/E were the most prevalent sub-genotypes and recombinant genotypes respectively (p < 0.0001). Finally, we observed a significant decrease in the prevalence of genotype E in west Africa over the years (p = 0.049) and a significant increase in the prevalence of sub-genotypes/recombinant genotypes over the years in north Africa (p = 0.036).

Historical and recent continental and intercontinental migrations can provide a plausible explanation for the HBV genotype, sub-genotype and recombinant genotype distribution pattern on the African continent.

Mapping

Genotypes

Sub-genotypes

Migrations

Recombinant genotypes

Hepatitis B virus (HBV), the key etiological agent for liver related diseases, is a member of the family Hepadnaviridae with a partial circular double stranded DNA(1)(2) and a genome size of 3.2 kb(3). It uses a reverse transcriptase enzyme during its replication similar to HIV leading to high genetic plasticity (4). Thus, to date, ten genotypes (A-J) have been reported using a divergence of ≥ 8% in the viral genome (2)(5). Genotype A has a pluralistic distribution globally, B and C are more frequent in Asia, D in southern Europe, E in Africa, F in United States of America, G in France while H in Central America. In contrast, the epidemiology of I and J is not well documented (6). The genotypes have been reported to influence the risk of infection, the course of the disease after acquisition of the infection and the response to anti-viral therapy (7). For example, poor response to interferon gamma (INF-γ) therapy among patients infected with the genotype C & D as opposed to A&B genotype infection has been highlighted (8). Similarly, poor prognosis among patients infected with the genotype C than those infected with the genotype B with a higher risk of progressing to hepatocellular carcinoma (HCC) has been reported (8). In contrast, some reports have implicated the genotype B than the genotype C in poor prognosis (6). Partaining genotypes and the HBV chronic infcetion, genotype A has been at the fore front of the chronic infection and the HCC in African cohort (9) when compared to other genotypes. Finally, infection with the genotype A has been reported to increase the possibility of non-response to the nucleotide/nucleoside analog antiviral therapy but rather good response to the interferon therapy (10). Accordingly, for countries where the chronic HBV infection is due to the genotype A, non-response to nucleoside/nucleotide therapy will be high and clinicians should use the interferons as the drugs of choice in management these patients(8).

The infecting genotypes also affects the viral replication rate and hence the HBV viral load. For example, the viral load during infcetion with the genotype C is higher than during infection with the genotype B. Similarly, infcetion with the genotype D presents with a higher viral load than the infection with the genotype A(11)(12)(13)(14). In addition, the infecting genotype will influence the course of the disease as well as the survival rate post-HCC treatment. For example, the infection with genotype C is associted with a high risk of progression to liver cancer and post-cancer treatmnet re-occurance than the infcetion with the genotype B or the genotype A(11)(12)(13)(14). Interestingly, the infection with genotype mixtures presents with an elevated viral load in an additive fashion than infection with a single genotype (15).

The genotypes have also been shown to influence the route of acquisition of the virus. For example, the HBV genotype A is associated with unprotected sexual intercourse between uninfected and an infected sexual partner, genotype D with transfusion of contaminated blood (16) (17), genotype G with homosexuals (18) while the genotypes B and C with mother-to-child transmission (19) (10) (20).

The HBV sub-genotypes also influence the clinical presentation during the HBV infection. For example, the HBV genotype C; sub-genotype C2, genotype B; sub-genotypes B2-B5 and genotype F; sub-genotype F1 have been reported to be associated with the rapid HCC development (21). Similarly, the HBV genotype A; sub-genotype A1 has been reported to be generally associated with a high risk of progression to HCC among the Bantu communities (9) whereas the sub-genotype A2 is associated with the development of the HCC among the elderly (21). However, little is known about the role of sub-genotype A3 and clinical profile of the disease. Further still, the HBV genotype C; sub-genotype C2 has been reported to be associated with higher risk of HCC than sub-genotype C1(22).

Unfortunately, the HBV genotype evaluation is not routine in many African countries despite their influence on the prognosis and clinical presentation of the disease. Therefore, the knowledge of infecting genotype can provide valuable information to the clinician during the management of the disease in chronic, acute and sub-acute infections. Thus, our study was primarily aimed at mapping the de novo genotype, sub-genotypes and genotype mixtures with evidence from historical and recent continental and intercontinental migrations. The results of the data synthesis have provided information to the stake holders involved in the management of the HBV about the distribution of the HBV genotypes, sub-genotypes and genotypes mixtures. In addition, the meta-analysis has provided constructive insights over a 25-year trend of genotype, sub-genotype and recombinant genotype pattern through meta-regression analysis from a large data base for regional specific management of HBV. This trend can be used to inform future research about the potential changes in the dynamics of HBV genotype, sub-genotype and recombinant genotypes patterns in Africa.

Systematic review protocol registration, information sources, and search strategies

The study was designed to map the circulating HBV genotypes, sub-genotypes and recombinant genotypes in Africa over a period of 25 years in tandem with migration trends. The findings of the survey have provided information to the health care givers and the policy makers on the plausible approached to address the pandemic with a goal of eliminating it by 2030 in accordance to the UN resolution(23). The survey protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO), University of York Centre for Reviews and Dissemination (https://www.crd.york.ac.uk/PROSPERO), under the registration number CRD42022300220. When we were conducting the systematic review and meta-analysis, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were critically followed. The systematic search was done from the reliable electronic data bases which included; Willy library, African Journal Online (AJOL), Scopus, PubMed, EMBASE, and Google Scholar. Throughout our search, the key terms highlighted in the Table 1 below guided us. We searched the key terms (Table 1) for the circulating HBV genotypes by region/country in titles ad or abstracts of the published article. In contrast, the data associated with the HBV sub-genotypes and recombinant genotypes were searched for in full-text of the article. We also reviewed the references of eligible articles to widen the scope of our search.

Table 1: Keywords used for searching in databases

Field searched	Key words
HBV genotypes	“HBV genotypes in Africa*”, “HBV genotypes by region OR country”, Circulating HBV genotypes in north Africa”, Circulating HBV genotypes in west Africa”, Circulating HBV genotypes in east Africa”, Circulating HBV genotypes in south Africa”,
HBV sub-genotypes	“HBV sub-genotypes in Africa*”, “HBV sub-genotypes by region OR country”, “HBV sub-genotypes in north Africa”, HBV sub-genotypes in west Africa”, “HBV sub-genotypes in east Africa”: HBV sub-genotypes in south Africa”,
HBV recombinant genotypes	“HBV recombinant genotypes in Africa*”, “HBV recombinant genotypes by region OR country”,

All phrases marked with a star covered all the possible variants of phrases and were used once. The keywords searched with “OR” were used twice during the search in the databases.

Journal article search strategy

Three researchers (HMK, AW, DN) performed the search in Google Scholar between February 10^th to 20^th 2022 using terms listed in table 1 above. Between February 21^st -28^th 2022, HMK, AW, HS and DN searched the Scopus database using the same terms. As previously reported, a snowball search was also carried out to detect additional studies by searching the references of the publications eligible for full text review using the Google scholar and Scopus to identify and screen the studies citing them. Between March 1^st to 8^th 2022, AW and HMK searched the PubMed data base using the aforementioned terms in table 2. As with the search from the Scopus database, a snowball search to identify additional studies by searching the references of the publications eligible for full text review using the Google scholar to identify and screen studies citing them was done. From 10^th to 17^th March, HMK, AW and DN searched in the AJOL database and, using the same strategy of snowball search, they also identified the studies from the references of the eligible studies. Similar searchers using the aforesaid strategies were conducted by HMK and AW in the Cochrane, the Willy libraries and EMBASE on March 21^st, 22^nd and 23^rd 2022 respectively. Finally, we updated the database search on March 28^th 2022 and the snowball using the same search strategy but narrowing the search to only 2015 onwards (Table 2).

Table 2: Databases consulted. Date of the search and period covered

Data base	Date the search was done	Period covered
Google Scholar	February 10^th to 20^th 2022	1997 to 2021
Scopus	February 21^st -28^th 2022	1997 to 2021
PubMed	March 1^st to 8^th 2022	1997 to 2021
AJOL	March 10^th to 17^th 2022	1997 to 2021
Cochrane	March 21^st2022	1997 to 2021
Willy libraries	March 22^nd2022	1997 to 2021
EMBASE	March 23^rd2022	1997 to 2021
All databases	March 28^th 2022	2015 to 2021

Selection of articles for meta-analysis

Exclusive review of the title, abstract and full paper was done by three reviewers (HMK, AW and DN). A consensus was sought to settle the disagreement by involving two additional reviewers (HS and PO) during the routine evaluation meetings in case of any incongruity between the primary reviewers. Duplicates were identified in the records through a full-text analysis and this was performed by HMK, AW and DN. Only the full-text articles were retained for data extraction. The other authors (CDK, EW, HK, DK and JES) supervised the work of HMK, AW and DN

Data extraction

Three authors (HMK, AW and DN) who searched and screened the records extracted the data. The data that were extracted included the first author, year of publication, study design, country, region, genotype, prevalence, patient type and genotyping method (Table 3).

Quality assessment

The assessment of the quality of each record was done by using the new Newcastle-Ottawa scale (24). This was done by three independent reviewers (HMK, AW and DN). The authors PO, HK and HS supervised the work of the HMK, AW and DN to ensure consistence in the quality of the work assessed. For quality evaluation, the three dimensions of comparability, selection and exposure as described in the Newcastle-Ottawa scale were considered for our quality analysis of the records. Each record was assigned a score which ranged from the worst of 0 to the best of 9. For a high-quality study, the score was 9-8, for a satisfactory study, the score was between 7-6 whereas for an unsatisfactory study, the score was ≤5 and was rejected.

Ethical approval

The data generated was from published studies that are already in the public domain, and probably the primary studies obtained ethical approval. Therefore, our study did not require ethical approval.

Statistical methods

The comparison of the relative proportions of the various genotypes with the independent variables of sub-regions was determined by the Z-test. The comparison of the relative proportions of the various genotypes with the independent variable of sub-regions was determined by the Z-test. The Meta-analysis of the relative prevalence of the emerging genotypes B and C on the African continent by region was evaluated by use of chi-square. The prevalence of sub-genotypes and genotype mixtures by country was evaluated by using Fisher’s exact test. The variations in the prevalence of dominant genotype, other genotypes and sub-genotypes/recombinant genotypes over the past 25 years on the continent was done by using meta-regression analysis. A p <0.05 was considered significant. Heterogeneity was evaluated by calculating the heterogeneity (I²) statistic and a value of 50% was used as the cutoff. For those pooled studies with I²≥50% and P _het < 0.1, random-effects model (DerSimonian and Laird method) was used to pool the proportions among the cases and the controls. For those pooled studies with I²<50% or P _het >0.1, the fixed effect models (Mantel–Haenszel method) were used(25). All analyses were performed by using the statistical software MedCalc version 20.010. The software called MedCalc version 20.010 was used for all the analyses.

Sub-group meta-analysis

Sensitivity analysis was done through sub-group meta-analysis. The sub-groups were genotypes, sub-genotypes and recombinant genotypes. These were evaluated by region, sub-region and over the 25 years.

Study selection and baseline characteristics

Based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and strategy, a total of 2,321 studies were retrieved from the searched databases; 587 from PubMed, 544 from Scopus, 15 from African Journal Online (AJOL), 693 from Google Scholar, 67 from Cochrane, 103 from Willy library and 312 from EMBASE. After removal of duplicates and screening all records, 60 studies meeting the previously described eligibility criteria were used in the meta-analysis. The article number and reason for exclusion in each screening steps are shown in Fig 1.

Overall, a sample of three thousand two hundred eighty-two (3,283) participants was pooled from 60 eligible studies for inclusion in our data synthesis. By region, 10 studies (27)(28)(29)(30)(31)(32)(33)(34)(35)(36) were from east Africa with a pooled sample size of 531, 7 studies (37)(38)(39)(40)(41)(42)(43) from north Africa with a pooled sample size of 621, 12 studies (44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55) from southern Africa with a pooled sample size of 483 and 31 studies (56)(57)(58)(59)(60) (61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85) (86) from west Africa with a pooled sample size of 1,648. By country, 23 countries out of the 54 African Union member countries (42.6%) had eligible studies for inclusion in the meta-analysis. One study was from each of the following countries; Cape Verde(84), Angola(47), Eretria(35), Guinea Bissau(63), Libya(38), Malawi(46), Mozambique(51), Rwanda(30) and Uganda(27) with sample sizes 96, 30, 122, 26, 60, 20, 9, 45 and 93 respectively.

Table 3: Characteristics of eligible studies.

First author, Year	Study design	Country	Region	Genotypes (n)	Sample	Patient type	Genotyping Method
de Pina-Araujo et al., 2018	Cross-sectional	Cape Verde	West Africa	D (1), A (75), E (19)	95	Community based	Sequencing
Fujiwara et al., 2005	Cross-sectional	Benin	West Africa	E (20), A (1)	21	Blood donors	RFLP
De Paschale et al., 2014	Prospective cohort	Benin	West Africa	E (19)	19	ANC women	INNO-LiPA
Diarra et al., 2018	Cross-sectional	Burkina Faso	West Africa	A (4), E (17)	21	Occult HBV	Sequencing
Compaore et al., 2016	Cross-sectional	Burkina Faso	West Africa	E (120)	120	HIV+ Cohort	Multiplex PCR
Candotti et al et al., 2016	Prospective cohort	Burkina Faso	West Africa	E (71), A (28)	99	Blood Donors	Sequencing
Lago et al., 2014	Cross-sectional	Angola	South Africa	E (30)	30	Staff and visitors of a private hospital	Sequencing
Anderson et al., 2018	Cross-sectional	Botswana	South Africa	A (12), D (12), E (1)	25	HIV+ Cohort	Sequencing
Choga et al., 2018	Cross-sectional	Botswana	South Africa	A1 (13), D3 (21), D2 (1) NT (1)	36	Blood donors	Sequencing
Matthews et al., 2015	Cross-sectional	Botswana	South Africa	A (14), D (2)	16	HIV+ Cohort	Sequencing
Angounda et al., 2016	Cross-sectional	DRC	East Africa	A (24), E (58)	82	CHBV	Sequencing
Shindano et al., 2018	Cross-sectional	DRC	East Africa	A (40), E (1)	41	Hospital attendees	Sequencing
Elmaghloub et al., 2017	Cross-sectional	Egypt	North Africa	D (3), D/E (4), E (7)	14	HCWs	Sequencing
Iman et al., 2010	Cross-sectional	Egypt	North Africa	D (87), D/F (17)	100	HBV patients	INNO-LiPA
Zekri et al., 2007	Cross-sectional	Egypt	North Africa	A (7), B (18), C (6), D (26), A/D (5), C/D (2), B/D (2), B/C (2) ND (2)	70	Pediatric HCC cohort	PCR and RFLP
Archampong et al., 2017	Cross-sectional	Ghana	West Africa	E (58), A4 (3), A1 (1), D8 (1)	63	HIV-HBV co-infected	Sequencing
Ampah et al et al., 2016	Prospective cohort	Ghana	West Africa	E (52)	52	Randomized volunteers	Sequencing
Boyce et al et al., 2017	Case report	Ghana	West Africa	D/E (3)	3	HIV-HBV co-infected	Sequencing
Candotti et al., 2006	Cross-sectional	Ghana	West Africa	A (10), D (3), E (87), A/E (1)	101	Blood donors	INNO-LiPA
Candotti et al et al., 2007	Cross-sectional	Ghana	West Africa	E (69), E (1)	70	Mothers and their neonates	Sequencing
Geretti et al et al., 2010	Cross-sectional	Ghana	West Africa	E (82), A (4)	86	HIV+	Sequencing
Huy et al et al., 2006	Cross-sectional	Ghana	West Africa	E (12)	12	Blood donors	Sequencing
Dongdem et al., 2016	Cross-sectional	Ghana	West Africa	A (8), D (3), E (47)	58	CHBV	RFLP
Honge et al., 2014	Cross-sectional	Guinea-Bissau	West Africa	E (25), D (1)	26	HIV+
Boyd et al et al., 2016	Prospective cohort	Ivory Coast	West Africa	E (98), A (2)	100	HBV-HIV co-infected	Not specified
Anders et al., 2016	Prospective cohort	Ivory Coast	West Africa	A (1), E (92)	93	HBV-HIV co-infected	PCR based methods
Suzuki et al., 2003	Cross-sectional	Ivory Coast	West Africa	A (3), D (3), E (42)	48	HBV carriers	Sequencing
Lawson-Ananissoh et al., 2017	Cross-section	Ivory Coast	West Africa	A (6), E (27)	33	CHBV patients	INNO-LiPA
Day et al., 2013	Cross-sectional	Kenya	East Africa	A (10)	10	HIV+ women on ART	Sequencing
Mabeya et al., 2017	Cross-sectional	Kenya	East Africa	A (11)	11	HIV+ patients	Sequencing
Mwangi et al., 2009	Cross-sectional	Kenya	East Africa	A (46), E (4), D (2)	52	Blood donors	Sequencing
Ochwoto et al., 2013	Cross-sectional	Kenya	East Africa	A (38), D (3), D/E (1)	42	Liver disease patients	Sequencing
Webale et al., 2015	Cross-sectional	Kenya	East Africa	A (33)	33	HIV1+ and un-HIV infected	Sequencing
Salem MA et al., 2012	Cross-sectional	Libya	North Africa	A (1), D (54), E (1), D/E (4)	60	HBV infected	INNO-LiPA
Traore et al et al., 2015	Cohort	Mali	West Africa	E (82), D/E (5), D4 (1), A3 (2)	90	HBV infected and liver disease patients	Sequencing
Cella et al et al., 2017	Cross-sectional	Mali	West Africa	E (16)	16	HBV infected	Sequencing
Sugauchi et al., 2003	Cross-sectional	Malawi	South Africa	A (20)	20	HBV chronic carriers	Sequencing
Mabunda et al., 2020	Cross-sectional	Mozambique	South Africa	A1 (8), E (1)	9	Occult HBV among blood donors	Sequencing
Chekaraou et al et al., 2010	Cross-sectional	Niger	West Africa	E (20), D/E (4)	24	Blood donors	Sequencing
Brah et al., 2016	Cross-sectional	Niger	West Africa	E (21), D/E (1), A3/E (1)	23	HBV infected	Sequencing
Ahmad et al., 2019	Cross-sectional	Nigeria	West Africa	A (2), B (1), E/B (82), A/B/C/E (22), E (21), E/B/A (7), E/B/C (2), D/B/A (1)	138	HBV carriers	Nested PCR
Ayodele et al., 2019	Cross-sectional	Nigeria	West Africa	B (5), E (10)	15	HBV-HIV co-infected	Sequencing
Faleye et al., 2015	Cross-sectional	Nigeria	West Africa	E (19), NT (3)	22	ANC mothers	Sequencing
Forbi et al., 2010	Cross-sectional	Nigeria	West Africa	E (53), A (2)	55	ANC mothers and HIV+	Sequencing
Opaleye et al et al., 2016	Cross-sectional	Nigeria	West Africa	E (17)	17	CHBV	Sequencing
Oyinloye et al., 2021	Cross-sectional	Nigeria	West Africa	B/E (9)	9	CHBV	Nested PCR
Hubschen et al., 2009	Cross-sectional	Rwanda	East Africa	A (30), B (1), C (4), D (10)	45	HIV+ women	Sequencing
Maylin et al et al., 2015	Cohort	Senegal	West Africa	A (22), E (65)	87	CHBV	Sequencing
Vray et al., 2006	Cross-sectional	Senegal	West Africa	A (9), E (23)	32	Blood donors	Affymetrix system
Bowyer et al., 1997	Cross-sectional	South Africa	South Africa	A (24), D (3), B (1), C (1)	29	CHBV and Acute HBV	Sequencing
Kew et al., 2005	Cross-sectional	South Africa	South Africa	A (172), D (35), E (3) ND (12), A1 (146)	222	HCC patients	PCR and RFLP
Makondo et al., 2012	Cross-sectional	South Africa	South Africa	A (28), D (1)	29		Sequencing
Maponga et al. 2020	Cross-sectional	South Africa	South Africa	A (34), D (7), E (1)	42	HCC patients	Real time PCR
Selabe et al., 2009	Cross-sectional	South Africa	South Africa	A (10), B (4), C (2), D (1)	17	CHBV	Sequencing
Gededzha et al., 2016	Cross-sectional	South Africa	South Africa	A (5), D (3)	8	HBV-HIV co-infected and uninfected	Sequencing
Ayed et al., 2006	Cross-sectional	Tunisia	North Africa	A (1), B (1), C (3), D (139), Mixed (20)	164	CHBV	INNO-LiPA
Bahri et al., 2006	Cross-sectional	Tunisia	North Africa	A (7), D (66), E (6), NT (4)	83	CHBV	RFLP
Hannachi et al., 2010	Cross-sectional	Tunisia	North Africa	D (125), A (5)	130	CHBV	TSP-PCR
Hamida et al., 2021	Cross-section	Eretria	East Africa	A (3), B (1), C (21), D (26), E (19), A/D (6), A/E (1), B/E (1), C/D (16), C/E (13), D/E (5), A/D/C (1), C/D/E (9)	122	Patients with liver disease	Multiplex-nested PCR
Zirabamuzale et al., 2016	Cross-sectional	Uganda	East Africa	A (16), D (47), E (1), A/D (6), A/D/E (3), A/D/E/G (1), A/E (9), B/C/D (1), D/E/G (1), D/E (2), D/G (3), Intermediate (3)	93	Delinked stored samples	INNO-LiPA

Two studies were from each of the following countries; Benin(86)(69), DRC(34)(32), Mali(72)(77), Niger(66)(82) and Senegal(56)(71) with pooled sample sizes of 30, 123, 106, 47 and 119 respectively. In addition, three studies each were reported from Botswana(48)(50)(49), Burkina Faso(78)(59)(74), Egypt(40)(39)(43) and Tunisia(42)(41)(37) with pooled sample sizes of 77, 240, 184 and 377 respectively. Finally, four studies with a pooled sample size of 274 were from Ivory Coast(80)(58)(61)(61), five studies with a sample size of 148 were reported in Kenya(31)(28)(33)(29)(36), six studies were conducted from each of Nigeria (75)(68)(81)(70)(79)(60)and South Africa (53)(87)(54)(44)(52)(55)with sample sizes of 256 and 347 respectively and, eight studies from Ghana(65)(67)(64)(57)(85) (76)(83)(73)with a sample size of 445. By year of publication, 27(45%) of the studies that were eligible for inclusion in our systematic review and meta-analysis were published between 2016 to 2021, 13(21.67%) between 2011 to 2015, 15(25%) between 2006 to 2010 and 5(8.3%) between 1997 to 2005. Regarding the genotyping method used, 40(66.67%) of the studies used sequencing, 8(13.3%) INNO LiPA, 7(11.67%) RFLP, 2(3.33%) real time PCR while 1(1.67%) study for each of nested PCR, Affymetrix system and Multiplex PCR (Table 3, Figure 2).

Relative prevalence of the hepatitis B genotypes in Africa

Our systematic review and meta-analysis have reported genotypes A-E as the circulating genotypes on the African continent. Overall, genotype E had the highest pooled prevalence of 71.2% from 45 eligible significantly higher than all the other genotypes (p<0.001, 95% CI= [56.512 to 83.943]). This was followed by genotype A from 42 eligible studies at a pooled prevalence of 40.581%; 95% CI= [28.407 to 53.373] and genotype D with a pooled prevalence of 24.942%; 95% CI= [13.547 to 38.459] from 25 studies. In contrast, genotypes B and C had the lowest prevalence of 19.739%; 95%CI= [1.923 to 49.624] from 8 studies and 10.674%; 95% CI= [4.716 to 18.665] from 6 studies respectively. For all the analyses, the heterogeneity remained high (I²>79%, p<0.05) and the random effect model (REM) was used to pool the genotype prevalence (Table 4, Figures 3 and 4).

Regional prevalence of the hepatitis B virus genotypes

When we disaggregated our data by regions, all genotypes, except genotype C in west Africa, were represented in all the regions with sufficient number of eligible studies for meta-analysis. However, there was a disproportionate distribution of the genotypes in these regions. In eastern Africa genotype A posted the highest pooled prevalence of 72.791%; 95%CI= [41.7 to 94.86] from 10 studies significantly higher than the prevalence of all other genotypes (p<0.0001). The heterogeneity of the included studies for the analysis was high (I²= 98.17%, 95%CI= [97.55 to 98.63], p<0.0001) and the random effect model was used for the analysis.

Table 4: Meta-analysis of the prevalence of the hepatitis B virus genotypes in Africa

Sub-groups			Analysis of HBV prevalence		Analysis of heterogeneity
Genotypes	No	Sample size	Prevalence %(95%CI)	P value	I2% (95%CI)	P het	Model
Genotype E	45	2800	71.2 (56.512 to 83.943) Ref		98.54 (98.35 to 98.71)	< 0.0001**	Random
Genotype A	42	2729	40.581 (28.407 to 53.373)	< 0.0001	97.84 (97.51 to 98.13)	< 0.0001**	Random
Genotype B	8	604	19.739 (1.923 to 49.624)	< 0.0001	98.34 (97.72 to 98.79)	< 0.0001**	Random
Genotype C	6	556	10.674 (4.716 to 18.665)	< 0.0001	85.10 (69.43 to 92.74)	< 0.0001**	Random
Genotype D	25	1946	24.942 (13.547 to 38.459)	< 0.0001	97.64 (97.18 to 98.02)	< 0.0001**	Random

Similarly, in southern Africa, our meta-analysis reported genotype A as the most highly circulating genotype with a pooled prevalence of 79.441%; 95% CI= [68.8 to 88.34] from 9 eligible studies significantly higher than the prevalence of any other genotype (p<0.0001). Statistical heterogeneity was observed among the included studies for the analysis (I²=77.94% 95% CI= [58.26 to 88.35], p<0.0001). In contrast, our meta-analysis reported genotype E as the most prevalent in west Africa with a pooled prevalence of 87.44%; 95% CI= [78.16 to 94.43] from 9 eligible studies significantly higher than all other genotypes (p<0.0001).

Table 5: Meta-analysis of the regional prevalence of the hepatitis B virus genotypes

Sub-groups			Analysis of HBV prevalence		Analysis of heterogeneity
Genotype	No	Sample size	Prevalence %(95%CI)	P value	I2% (95%CI)	P het	Model
East Africa
Genotype A	10	531	72.791 (41.7 to 94.86) Ref		98.17 (97.55 to 98.63)	< 0.0001**	Random
Genotype B	2	167	1.632(0.307 to 4.889)	< 0.0001	0.00(0.00 to 0.00)	0.4183	Fixed
Genotype C	2	167	15.192(10.141 to 21.507)	< 0.0001	42.20 (0.00 to 0.00)	0.1884	Fixed
Genotype D	5	354	19.638(6.564 to 37.508)	< 0.0001	92.92(86.43 to 96.30)	< 0.0001	Random
Genotype E	5	390	15.440 (0.819 to 43.183)	< 0.0001	97.43 (95.85 to 98.41)	< 0.0001**	Random
South Africa
Genotype A	9	408	79.441 (68.8 to 88.34) Ref		77.94 (58.26 to 88.35)	< 0.0001**	Random
Genotype B	2	46	12.638(0.481 to 37.349)	< 0.0001	75.41(0.00 to 94.43)	0.0437	Random
Genotype C	2	46	7.720 (2.003 to 19.176)	< 0.0001	10.76 (0.00 to 0.00)	0.2898	Fixed
Genotype D	8	388	17.248 (10.042 to 25.917)	< 0.0001	67.36 (31.21 to 84.51)	0.0032	Random
Genotype E	5	328	26.662(1.717 to 66.518)	< 0.0001	97.32(95.66 to 98.35)	< 0.0001	Random
West Africa
Genotype E	30	1669	87.44 (78.16 to 94.43) Ref		96.19 (95.33 to 96.89)	< 0.0001**	Random
Genotype A	17	1238	13.283 (5.739 to 23.338)	< 0.0001	95.41 (93.86 to 96.56)	< 0.0001**	Random
Genotype B	2	153	11.832(2.578 to 57.786)	< 0.0001	93.64(79.48 to 98.03)	0.0001	Random
Genotype D	5	328	3.746 (1.979 to 6.387)	< 0.0001	0.00 (0.00 to 79.74)	0.4247	Fixed
North Africa
Genotype D	7	621	75.074 (58.01 to 88.85) Ref		95.07 (92.03 to 96.95)	< 0.0001**	Random
Genotype E	3	157	13.758(1.353 to 35.991)	< 0.0001	89.54(71.8 to 96.13)	0.0001**	Random
Genotype C	2	234	4.774(0.391 to 13.618)	< 0.0001	80.66(17.29 to 95.48)	0.0230	Random
Genotype B	2	234	9.459 (1.435 to 45.997)	< 0.0001	97.42 (93.53 to 98.97)	< 0.0001**	Random
Genotype A	5	507	4.510 (1.530 to 8.958)	< 0.0001	75.52 (39.89 to 90.03)	0.0026**	Random

For all the included studies, there was statistical heterogeneity (I²=96.19%; 95% CI= [95.33 to 96.89], p<0.0001) and the random effect model was used to pool the prevalence. In north Africa, genotype D reported the highest pooled prevalence of 75.074%; 95% CI= [58.01 to 88.85] from 7 eligible studies. The statistical heterogeneity was found among the included studies (I²=95.07% CI= [92.03 to 96.95], p<0.0001) and the random effect model was used to pool the prevalence (Table 5, Figure 5).

Furthermore, we compared the relative prevalence of the two emerging genotypes B and C on the African continent by region. Although the published data on these emerging genotypes is still limited, our results have shown that the prevalence of genotype B was significantly higher in southern Africa than eastern Africa (X²=11.299, p=0.0008, 95%CI= [3.472% to 23.5976]). In contrast, the prevalence of genotype C was significantly higher in eastern Africa than in northern Africa (X²=13.062, p=0.0003, 95%CI= [4.6197% to 16.968]) (Table 6).

Table 6: Meta-analysis of the relative prevalence of the emerging genotypes B and C on the African continent by region

Genotype	Region	No	Sample size	Prevalence %(95%CI)	X²	P value (95%CI)
B	South Africa	2	46	12.638(0.48 to 37.349) ref
	East Africa	2	167	1.632(0.307 to 4.889)	11.299	0.0008(3.472% to 23.5976)
	West Africa	2	153	11.832(2.578 to 57.786)	0.0216	0.8831(-8.3008% to 14.04)
	North Africa	2	243	9.459 (1.435 to 45.997)	0.434	0.5100(-4.872% to 16.093)
C	East Africa	2	167	15.192(10.14 to 21.51) ref
	South Africa	2	46	7.720 (2.003 to 19.176)	1.708	0.1913(-4.799% to 15.352)
	North Africa	2	243	4.774(0.391 to 13.618)	13.062	0.0003(4.6197% to 16.968)

Prevalence of the sub-genotype by country.

The prevalence of sub-genotypes by country was evaluated by using Fisher’s exact test because of the scant published data on the prevalence of the sub-genotypes in Africa. Hence, we had insufficient data to pool the prevalence of the sub-genotypes because only one eligible study was obtained for each sub-genotype except for genotype A1 with four eligible studies. Besides, data on sub-genotypes was only available for published studies from four countries which included Botswana, Ghana, Mali and Mozambique. Overall, sub-genotype A1 was the most prevalent in proportions higher than any other sub-genotype (168/222, 75.7%) (p<0.05). (Table 7, Figure 3).

Table 7: Prevalence of the sub-genotypes by country

Sub-genotype	Country	Number of studies	Prevalence	Sample size (% prevalence)	Fisher’s test p value
A1	Ghana, Botswana, Mozambique, South Africa	4	168	222(75.7) Ref
D3	Botswana	1	21	36(58.3)	<0.0001*
A3	Mali	1	2	90(2.2)	<0.0001*
A4	Ghana	1	3	63(4.8)	<0.0001*
D2	Botswana	1	1	36(2.8)	<0.0001*
D4	Mali	1	1	90(1.1)	< 0.0001*
D8	Ghana	1	1	63(1.6)	<0.0001*

*P value of sub genotype prevalence with respect to the reference sub genotype < 0.05 statistically significant

Prevalence of genotype mixtures

We evaluated the prevalence of the genotype mixtures on the African continent by using the Fishers exact test. Data was available from only nine countries. The prevalence of the genotype mixture B/E reported from Nigeria and Eretria (93/269, 34.2%) was significantly higher than the prevalence of the other genotype mixture (p<0.05). Interestingly, recombinant genotype D/E was the most diverse reported by 9 studies in eight countries followed by A/E and A/D from 4 and 3 studies respectively (Table 7).

Table 7: Recombinant/mixed genotype prevalence by country

Genotype mixtures	Country	No	Prevalence	Sample size (% prevalence)	Fisher’s test p value
B/E	Eretria, Nigeria	3	93	269(34.2)
A/B/C/E	Nigeria	1	22	138(15.9)	0.003*
A/D/C	Eretria	1	1	122(0.82)	< 0.0001*
A/D/E	Uganda	1	3	93(3.2)	< 0.0001*
B/C/D	Uganda	1	1	93(1.1)	< 0.0001*
C/D	Egypt	1	2	70(2.9)	< 0.0001*
C/D/E	Eretria	1	9	122(7.4)	< 0.0001*
C/E	Eretria	1	13	122(10.7)	< 0.0001*
D/B/A	Nigeria	1	1	138(0.7)	< 0.0001*
D/E/G	Uganda	1	1	93(1.1)	< 0.0001*
D/F	Egypt	1	17	100(17.0)	0.012*
D/G	Uganda	1	3	93(3.2)	< 0.0001*
D/E	Egypt, Ghana, Kenya, Libya, Mali, Niger, Eretria, Uganda	9	29	471(6.2)	< 0.0001*
A/E	Uganda, Eretria, Ghana, Niger	4	12	339(3.5)	< 0.0001*
A/D	Egypt, Eretria, Uganda	3	14	285(4.9)	< 0.0001*
E/B/A	Nigeria	1	7	138(5.1)	< 0.0001*
E/B/C	Nigeria	1	2	138(1.5)	< 0.0001*

*P value of recombinant/mixed genotype prevalence with respect to the reference recombinant genotype < 0.05 statistically significant

Variation in the HBV dominant genotypes, other genotypes, sub-genotypes and recombinant genotypes.

We performed a meta-regression analysis on the variations in the dominant genotype over the past 25 years on the continent. Our results reported a general decline in the genotypes known to be dominating in the respective regions. However, the decline was only statistically significant in western Africa (r=0.36, p=0.049). Similarly, by meta-regression analysis of the variation in the prevalence of other genotypes other than the dominant genotype over the years, there was increase in the prevalence of these genotypes (Figure 6).

Non the less, the increase was not statistically significant (p>0.05) although a positive correlation was observed. Finally, meta-regression analysis of the variation in the prevalence of sub-genotypes/recombinant genotypes over the years only significantly increased in north Africa (r=0.9, p=0.036) (Figures 7 and 8).

Table 8: Role of intra and inter-continental migrations in the apparent distribution of HBV genotypes in Africa

Genotype(s)	Migrations
A and E in eastern and southern Africa	Ancient pastoral communities from eastern Africa to central-southern Africa(88) Ancient farmers migrations from western Africa to southern-eastern Africa(89) Migrations of labourers from West Africa to Congo to construct the Congo railway during the colonial times(90) Bantu-speaking farmers migrations from western-central Africa around Niger and Benue rivers across central Africa to the southern-eastern Africa due to desertification pressure around 4,000 years ago(91) Migrations from west Africa to south Africa for employment and education (92)
D in North Africa	Immigrations of French and Italians into north Africa during the transoceanic immigrations(93)
B and C in Africa	Trans-continental migrations from south east Asia and the far East into Eastern and southern Africa(92) Colonialist immigrants from Europe to eastern and southern Africa during African colonization(94)(95). Migrations of Asians to east Africa during the construction of the east Africa railway(96). Business and education trips to and from Asia(96)

We obtained the data on the HBV genotypes, sub-genotypes and recombinant genotypes from only 23 (42.6%) countries out of the 54 African Union member countries(97). Thus, even though the HBV prevalence is hyperendemic in most African countries, the data on the circulating genotypes is still scanty in literature. The HBV genotypes influence the clinical presentation of the disease, mutations rates, response to therapy, viral replication kinetics and transmission dynamics(7)(2)(98)(14)(16), so establishing the circulating HBV genotypes at local, sub-region and regional level should be of prime attention by all health systems since HBV is a trans-boundary disease.

Our results have shown that along the south-eastern Africa corridor, genotype A is the most predominant consistent with the findings by(93) from their meta-analysis on the global distribution of HBV genotypes. Similarly, genotypes E and D are the most prevalent in western and northern Africa respectively consistent with the findings of (93).

The underlying reasons for the differences in the prevailing genotypes by regions are not fully understood. In the current study, we have explored the role of the intra and inter-continental migrations to account for the differential distribution of HBV genotypes in Africa as highlighted in literature. The figure 9 and table 8 give the summary of the migration routes and they have been comprehensively described to elucidate the plausible differences in the genotypes by region.

Pertaining the distribution pattern of the HBV/A genotype in eastern and southern Africa, these have been linked to historical migrations as highlighted by the Y-chromosome and archeological data. Firstly, the Y-chromosome genetic data has highlighted migration patterns of the ancient pastoral communities from eastern Africa to central-southern Africa (88). Secondly, the archeological data shows that the beads similar to those seen in southern Africa have been recently reported at the Panga ya Saidi cave site in Kenya(89). Thus, the HBV/A genotype probably has its origin from east Africa and could have been imported to southern Africa by the Bantu immigrants. Besides, genotype A has had a long history with the Bantu speakers of southern-Africa and it has been allied with progression to HCC among the chronically infected HBV persons belonging to the Bantu ethnic group (44).

In contrast, the high prevalence of genotype D in north Africa could be accounted for by its dominance in the Mediterranean region as well as in Europe. Hence, the historical immigrations of over 3 million French and Italians into north Africa during the transoceanic immigrations (93) could have imported genotype D in north Africa. Furthermore, the most dominant genotype in Europe is D (99). This could have been importation from Europe during the colonial times to north Africa or the Europeans could have imported it from north Africa.

Although genotype E has been reported to be the most dominant in west Africa, its prevalence elsewhere cannot be underestimated. For example, our results have shown that it is the second most predominant genotype in south Africa and north Africa but third in east Africa. This suggests that immigrants from west Africa have played an important role in the introduction of the de novo genotype E elsewhere on the continent (100). This idea is further confirmed by the recently reported migrations from west Africa to south Africa for employment and education (92). In addition, historical migrations from west Africa to south Africa have been documented. These include; first the recruitments from the British west Africa to Congo of labourers to construct the Congo railway during the colonial times (90). Secondly, the desertification pressure caused historical migrations of some Bantu-speaking farmers to move from their cradle land in western-central Africa around Niger and Benue rivers across central Africa to the southern-eastern Africa (91). Most importantly, our results have demonstrated that the prevalence of genotype E in west Africa has been decreasing over the past 25 years and is progressively being replaced by other genotypes A, B and D. Therefore, our results suggest that management strategies of HBV in west Africa should focus on a holistic approach involving a wide array of genotypes rather than focusing of genotypes E in isolation since each genotype presents with unique disease profile.

The progressive increase in the prevalence of genotypes B and C observed in our study is interesting because earlier studies have reported genotypes B and C to be confined in south east Asia and the far East respectively(101)(102). This explains the increased potential of trans-continental transmission of the HBV genotypes which can ultimately change the pattern of the disease profile among those infected by non-endemic genotypes. Specifically, our results have shown that genotype B was significantly higher in south Africa than East Africa probably because of the higher migrations of Asians to south Africa than to east Africa. Furthermore, this phenomenon, would suggest more interactions among the blacks in south Africa with the whites than in east Africa. Moreover, the influence of colonialism and white dominance was higher in south Africa than in eastern Africa(94)(95). Similarly, the significantly higher prevalence of genotype C in eastern Africa than north Africa could be explained by the more rampant migrations of Asians to east Africa than to north Africa dating back from the time of construction of the east Africa railway. In addition, business and education trips among Africans to and from Asia could potentially explain the observed trends in the prevalence of genotypes B and C in Africa(96)

The dominance of particular genotypes by region has public health concerns. For example, the community transmission of genotype A is mainly through unprotected sex (16). This suggests an un met need towards practicing safe sex in the regions where this genotype is predominant. Genotype E has been associated with mother to child transmission(103)(104). Thus, its high prevalence presupposes an un met need towards screening for HBV during antenatal care increasing the risk of mother-to-child transmission of HBV (105). Finally. genotype D is associated with blood transfusion(16). Probably there could be an unmet need towards safe blood transfusion region in regions dominated by this genotype. Interestingly, particular genotypes present with peculiar clinical disease profile. For example, genotype A has frequently been associated with chronicity and progression to HCC (98) (44). Thus, in regions where the patients are predominantly infected with HBV/A genotype, there is a high risk of progression to HCC. In contrast, HBV/D genotype infection has not been reported to be associated with aggressive disease like cirrhosis and HCC (106) although the findings vary with ethnicity (107). Finally, the response the HBV anti-viral therapy has been reported to be genotypes specific. For example, patients infected with genotypes A have been seen to respond better to interferon therapy but resistant to nucleoside analogs (98) (44). Thus, in regions where the patients are chronically infected with HBV/A genotype the treatment regimen of choice should be interferon rather than nucleoside analogs.

Concerning the emergency of genotypes B and C in Africa, the stewardship of HBV management needs to be re-focused in order to address these novel genotypes. They always present with particular clinical disease profile and the management of the affected patients should be allied towards the unique disease profile. For example, genotype C has been associated with poorer prognosis than B with a higher risk of hepatocellular carcinoma (HCC) among patients infected with genotype C (108)(8)(109). In addition, genotype C has been reported elsewhere as the most deadly genotype among all the HBV genotypes due to its association with high HBV DNA, high viremia, prolonged HBeAg seropositivity and BCP mutations that correlate with high risk of HCC(21). Furthermore, infection with genotype B has been reported to be associated with better response to anti-viral drugs, reduced viral load and an increased likelihood of HBeAb seroconversion than any other genotype than genotype C(98).

Pertaining the prevalence of sub-genotypes, a significantly higher prevalence of HBV/A1 in many countries compared to any other sub-genotype has been observed in our study. This observation should not be taken lightly when managing CHB patients because HBV/A1 has been associated with HCC among the HBV chronic carries of genotype A(9). The predominance of sub-genotype A1 in southern Africa observed in our study is not surprising since it has been earlier reported(44)(110). However, the emergency of the HBV/A1 in western Africa is novel(110) and deserves utmost attention. So, whereas among the Bantu speakers of south Africa, sub-genotype A1 has been implicated in accelerating the progression to HCC(44), its fate among the ethnic groups in west Africa is yet to be established. Thus, our results suggest that longitudinal studies involving follow of the carries of sub-genotype A1 in western Africa be conducted to elucidate the long-term effect of infection with this l sub-genotype in this region. The clinical profile among carries of sub-genotypes A2, A3 and A4 observed in our study are not well characterized. However, elsewhere, A2 has been associated with progression to HCC among the elderly(21). In our study, four HBV/D sub-genotypes have been highlighted; HBV/D2, D3, D4 and D8. Of all these HBV/D sub-genotypes, D3 has been the most characterized elsewhere. For example, it has been associated with decrease in the prevalence of CHB through LC to HCC (111), occult hepatitis B (OHB) infection that presents with reduced HBsAg shedding(112) and PreS2 ORF mutations with decreased risk of infection(112). Whether these findings are in conformity with the clinical profile during infection with D3 sub-genotypes among the African population lies in successful design of longitudinal studies to follow the prognosis among HBV/D3 CHB infected persons in an African Cohort. However, drawing conclusions from studies outside Africa on this subject would be elusive since a genetic component is highly implicated in clinical profile during HBV infection(113)

Recombinant genotypes have also been reported in our study which are suggestive of concomitant infection with two or more genotypes in the same patient. The recombinant genotypes, B/E was the most predominant and its prevalence was significantly higher than any other genotype mixture reported in our study. Similarly, the recombinant genotype D/E was the most cosmopolitan. These results should not be taken lightly in the management of the infections. The HBV-B/E has been reported to present with a more severe disease than either genotype B or E (96). Similarly, the wide distribution of the recombinant genotype D/E has serious public health concerns since it is associated with elevated viral load and high HBV infectivity(114)(115). The other recombinant genotypes were reported in isolated studies which however were spanning from southern Africa, eastern Africa, western Africa and northern Africa. Interestingly, our results have shown that the prevalence of recombinant genotypes has been on the increase in north Africa over the past 25 years. Elimination of risky behaviors associated with the co-infection with multiple genotypes should be implemented to avert their effects because their management is more stringent than managing patients with HBV genotype mono-infection.

In conclusion, our systematic review and meta-analysis has provided an updated literature on the current epidemiology of hepatitis B virus genotypes, sub-genotypes and recombinant genotypes on the African continent. Intercontinental, local and histological migrations as evidenced from literature can provide plausible conclusions to guide in the mapping of the HBV genotypes on the continent. Our analysis has shown that overall, genotypes E is the most dominant genotypes on the continent and is progressively becoming pluralistic despite its previous localization to west Africa. In addition, genotypes previously known to be restricted to Asia and Europe particularly B and C are also continuously being reported in isolated studies on the continent. These genotypes present with some of the most aggressive liver diseases including cirrhosis, fibrosis, HCC and liver decompensation. With the weak health systems in most of the countries on the African continent, emergency of these genotypes comes along with unique challenges in the management of HBV in Africa. Thus, African governments have to remain steady fast in their stewardship to manage yet more HBV liver related disease amidst the escalating other non-communicable diseases like hypertension and diabetes mellitus previously little known to be health burdens in Africa. The emergency of multiple genotype infections (mixed genotypes) is a marker of engagement in multiple risky behaviors that expose people to several genotypes like having multiple sexual partners. Thus, there is an un met need towards faithfulness and practicing safe sex despite the mass campaign against these vices in an HIV era. Finally, the sub-genotype A1 associated with HCC among the Bantu ethnic group of south, east and central Africa has found its way in west Africa whose clinical profile is yet to be elucidated.

Our study could not go without limitations. First, most of the data was extracted from cross-section studies which are associated with selection bias. Secondly, there is still scant published work on the prevalence of HBV genotypes, sub-genotypes and recombinant genotypes in Africa to give robust data for satisfactory conclusions to be drawn. Thus, we obtained data from only 23 African countries. Thirdly, most of the primary studies had small sample sizes owing to the associated high cost of genetic studies in resource remitted settings compromising the statistical power. None the less, we pooled the prevalence to raise the power for more reliable conclusions.

Ethics approval and consent to participate

Not applicable

Consent for publication

Not applicable.

Availability of data and material

All data generated or analyzed during this study are included in this published article and as supplementary materials

Competing interests

The authors declare that they have no competing interests.

Funding

The authors declare that they did not receive any specific funding for the study.

Authors' contributions

HMK and HS conceived the idea. HMK, AW, EK and AK participated in the data presentation, analysis and discussion. HMK wrote the final manuscript draft. All the authors reviewed the manuscript draft and approved the publication of the manuscript.

Authors’ information:

HMK is a molecular immunologist and virologist working on molecular immunology during hepatitis B virus infection targeting an African population. DN is an immunologist and biochemist with a PhD in Biochemistry and immunology. HS holds a PhD in Biochemistry & is a physician in the Department of Microbiology Makerere University working on molecular markers of drug resistance in HIV and malaria infections. PO is a physician with a PhD in gastroenterology and is an associate professor of gastroenterology with a lot of expertise in liver diseases working in the department of Medicine College of Health Sciences, Makerere University. AW is a microbiologist and immunologist working on anti-microbial resistance. HK and DK are lectures in the School of Biomedical Sciences, College of Health Sciences in the departments of Microbiology and Immunology respectively. CDK, EW, are lectures in the college of veterinary medicine animal resources and biosecurity (COVAB) in the school of Biolab and Biomolecular Resources. JES and DN are lecturers in the department of Plant Sciences, Microbiology and Biotechnology, College of Natural Sciences, Makerere University.

Acknowledgements

We are grateful to ICT system management at Islamic University in Uganda- Kampala Campus for allowing us to access the database. We also thank Dr. Ntanda K Moses, Makerere University College of Computing and Information Sciences for the ICT technical support.

Matsuura, K., Tanaka, Y., Hige, S., Yamada, G., Murawaki, Y., Komatsu, M., … Mizokami M. Distribution of hepatitis B virus genotypes among patients with chronic infection in Japan shifting toward an increase of genotype A. J Clin Microbiol. 2009;47(5):1476–1483.
Kurbanov, F., Tanaka, Y., & Mizokami M. Geographical and genetic diversity of the human hepatitis B virus. Hepatol Res. 2010;40:14–30.
Faure E. Alternative peptide-fusion proteins generated by out-of-frame mutations, just upstream ORFs or elongations in mutants of Human Hepatitis B Viruses. Virus Res. 2006;117:185–201.
Olinger C, Venard V, Njayou M, Oyefolu A, Maiga I, Kemp A, et al. Phylogenetic analysis of the precore/core gene of hepatitis B virus genotypes E and A in West Africa: new subtypes, mixed infections and recombinations. J Gen Virol. 2006;87:1163–1173.
Kurbanov F, Tanaka Y, Mizokami M. Geographical and genetic diversity of the human hepatitis B virus. Hepatol Res. 2010;40:14–30.
Sanchez-Tapias J, Costa J, Mas A, Bruguera M, Rodes J. Influence of hepatitis B virus genome on the long-term outcome of chronic hepatitis B virus in western patients. Gastroenterology. 2002;123:1848–56.
Matsuura K, Tanaka Y, Hige S, Yamada G, Murawaki Y, Komatsu M, et al. Distribution of hepatitis B virus genotypes among patients with chronic infection in Japan shifting toward an increase of genotype A. J Clin Microbiol. 2009;47(5):1476–83.
Wai C, Chu C, Hussain M. HBV genotype B is associated with better response to interferon therapy in HBeAg (+) chronic hepatitis than genotype C. Hepatol Hepatol. 2002;36:1425–30.
Kew MC, Kramvis A, Yu MC, Arakawa K, Hodkinson J. Increased Hepatocarcinogenic Potential of Hepatitis B Virus Genotype A in Bantu-Speaking Sub-Saharan Africans. 2005;521(November 2004):513–21.
Erhardt A, Blondin D, Hauck K, Sagir A, Kohnle T, Heintges T. Response to interferon alfa is hepatitis B virus genotype dependent: genotype A is more sensitive to interferon than genotype D. Gut. 2005;54:1009–13.
Yang H, Lu S, Liaw Y, You S, Sun C, Wang L. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med. 2002;347(168–174).
Iloeje U, Yang H, Su J, Jen C, You S, Chen C. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006;130:678–86.
Chen C, Yang H, Su J, Jen C, You S, Lu S. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295:65–73.
Yousif M, Kramvis A. Genotype D of hepatitis B virus and its subgenotypes: An update. Hepatol Res. 2013;48.
Nguyen L, Le H, Kremser P, Duy D, Vu Q, Koeberlein B, et al. Impact of the Hepatitis B Virus Genotypes and Genotype Mixtures on the Course of Liver Disease in Vietnam. Hepatology. 2006;43(6):1375–84.
Halfon P, Bourlie` re M, Pol S, Benhamou Y, Ouzan D, Rotily M. Multicentre study of hepatitis B virus genotypes in France: correlation with liver fibrosis and hepatitis B e antigen status. J Viral Hepat. 2006;13:329–35.
Koedijk F, van Houdt R, Op de Coul E, Dukers N, Niesters H, Mostert M, et al. Hepatitis B virus transmission patterns in the Netherlands, 2004. Ned Tijdschr Geneeskd. 2008;152:2673–80.
Sa´nchez L, Tanaka Y, Maldonado M, Mizokami M, Panduro A. Difference of hepatitis B virus genotype distribution in two groups of Mexican patients with different risk factors. High prevalence of genotype H and G. Intervirology. 2007;50:8–15.
Guo P, Zhong M, Hou J. Genotyping study of hepatitis B virus in its intrauterine transmission. Di Yi Jun Yi Da Xue Xue Bao. 2002;22:303–5.
Inui A, Komatsu H, Sogo T, Nagai T, Abe K, Fujisawa T. Hepatitis B virus genotypes in children and adolescents in Japan: before and after immunization for the prevention of mother to infant transmission of hepatitis B virus. J Med Virol. 2007;79:670–5.
McMahon B. The influence of hepatitis B virus genotype and subgenotype on the natural history of chronic hepatitis B. Hepatol Int. 2009;3(2):334-42.
Chan H, Tse A, Mo F, Koh J, Wong V, Wong G. High viral load and hepatitis B virus subgenotype Ce are associated with increased risk of hepatocellular carcinoma. J Clin Oncol. 2008;26(2):177–182.
WHO Sdg. World Health Organization. World health statistics 2016: monitoring health for the SDGs sustainable development goals. , 2016. 2016;
Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assesment of the quality of non-randomised studies in meta-analysis of genome searches. Genet Epidemiol,. 2010;25:603–5.
Zintzaras E. Heterogeneity testing in meta-analysis of genome searches. Genet Epidemiol. 2005;28:123–7.
Egger M S, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.
Zirabamuzale JT, Opio CK, Bwanga F, Seremba E, Apica BS, Colebunders R, et al. Hepatitis B virus genotypes A and D in Uganda. J Virus Erad [Internet]. 2016;2(1):19–21. Available from: https://doi.org/10.1016/S2055-6640(20)30693-2
Mwangi J, Nganga Z, Songok E, Kinyua J, Lagat N, Muriuki J, et al. Molecular genetic diversity of hepatitis B virus in kenya. Intervirology. 2009;51(6):417–21.
Day SL, Odem-Davis K, Mandaliya KN, Jerome KR, Cook L, Masese LN, et al. Prevalence, Clinical and Virologic Outcomes of Hepatitis B Virus Co-Infection in HIV-1 Positive Kenyan Women on Antiretroviral Therapy. PLoS One. 2013;8(3):1–5.
Hubschen J, Mugabo J, Peltier C, Karasi J, Muller P. Exceptional Genetic Variability of Hepatitis B Virus Indicates That Rwanda Is East of an Emerging African Genotype E/A1 Divide. J Med Virol. 2009;81::435–440.
Ochwoto M, Chauhan R, Gopalakrishnan D, Chen CY, Ng’ang’a Z, Okoth F, et al. Genotyping and molecular characterization of hepatitis B virus in liver disease patients in Kenya. Infect Genet Evol [Internet]. 2013;20(November 2018):103–10. Available from: http://dx.doi.org/10.1016/j.meegid.2013.08.013
Angounda BM, Ngouloubi GH, Dzia AB, Boumba LMA, Baha W, Moukassa D, et al. Molecular characterization of hepatitis B virus among chronic hepatitis B patients from Pointe Noire, Republic of Congo. Infect Agent Cancer [Internet]. 2016;11(1):1–8. Available from: http://dx.doi.org/10.1186/s13027-016-0088-3
Mabeya SN, Ngugi C, Lihana RW, Khamadi SA, Nyamache AK. Predominance of Hepatitis B Virus Genotype A among Treated HIV Infected Patients Experiencing High Hepatitis B Virus Drug Resistance in Nairobi, Kenya. AIDS Res Hum Retroviruses. 2017;33(9):966–9.
Shindano TA, Horsmans Y, Kabamba BM. Genetic and phylogenic characterization of hepatitis B virus in the eastern part of the Democratic Republic of Congo. J Med Virol. 2018;90(2):250–4.
Hamida ME, Raja SM, Petros Y, Wahab M, Seyoum Y, Elkhidir IM, et al. Prevalence of hepatitis B virus genotypes among patients with liver disease in Eritrea. Sci Rep [Internet]. 2021;1–8. Available from: https://doi.org/10.1038/s41598-021-90836-w
Webale M, Budambula V, Lihana R, Musumba F, Nyamache A, Budambula N. Hepatitis B virus sero-profiles and genotypes in HIV-1 infected and uninfected injection and Non-injection drug users from coastal Kenya. BMC Infect Dis. 2015;15:299.
Ayed K, Gorgi Y, Ayed-Jendoubi S, Aouadi H, Sfar I, Najjar T, et al. Hepatitis B virus genotypes and precore/core-promoter mutations in Tunisian patients with chronic hepatitis B virus infection. J Infect. 2007;54(3):291–7.
Salem MA, Elnifro EM, Alshuwen F. Molecular analysis of hepatitis B virus isolates in Libya: predominant circulation of hepatitis B virus genotype D. J Gastroenterol Hepatol Res. 2012;1(7):119–21.
Khaled IAEA, Mahmoud OM, Saleh AF, Bioumie EE. Prevalence of HBV genotypes among Egyptian hepatitis patients. Mol Biol Rep. 2011;38(7):4353–7.
Zekri ARN, Hafez MM, Mohamed NI, Hassan ZK, El-Sayed MH, Khaled MM, et al. Hepatitis B virus (HBV) genotypes in Egyptian pediatric cancer patients with acute and chronic active HBV infection. Virol J. 2007;4:1–7.
Bahri O, Cheikh I, Hajji N, Djebbi A, Maamouri N, Sadraoui A, et al. Hepatitis B genotypes, precore and core promoter mutants circulating in Tunisia. J Med Virol. 2006;78(3):353–7.
Hannachi N, Fredj N Ben, Bahri O, Thibault V, Ferjani A, Gharbi J, et al. Molecular analysis of HBV genotypes and subgenotypes in the Central-East region of Tunisia. Virol J. 2010;7:1–6.
Elmaghloub R, Elbahrawy A, Didamony G El, Elwassief A, Saied Mohammad A-G, Alashker A, et al. Hepatitis B virus genotype E infection among Egyptian health care workers. J Transl Intern Med. 2017;5(2):100–5.
Kew MC, Kramvis A, Yu MC, Arakawa K, Hodkinson J. Increased hepatocarcinogenic potential of hepatitis B virus genotype A in Bantu-speaking sub-saharan Africans. J Med Virol. 2005;75(4):513–21.
Maponga TG, Glashoff RH, Vermeulen H, Robertson B, Burmeister S, Bernon M, et al. Hepatitis B virus-associated hepatocellular carcinoma in South Africa in the era of HIV. BMC Gastroenterol. 2020;20(1):1–9.
Sugauchi F, Orito E, Kato H, Suzuki S, Kawakita S, Sakamoto Y, et al. Genotype, serotype, and phylogenetic characterization of the complete genome sequence of hepatitis B virus isolates from Malawian chronic carriers of the virus. J Med Virol. 2003;69(1):33–40.
Lago B V., Mello FC, Ribas FS, Valente F, Soares CC, Niel C, et al. Analysis of complete nucleotide sequences of angolan hepatitis B virus isolates reveals the existence of a separate lineage within genotype E. PLoS One. 2014;9(3).
Matthews PC, Beloukas A, Malik A, Carlson JM, Jooste P, Ogwu A, et al. Prevalence and characteristics of hepatitis B virus (HBV) coinfection among HIV-Positive women in South Africa and Botswana. PLoS One. 2015;10(7):1–11.
Anderson M, Choga WT, Moyo S, Bell TG, Mbangiwa T, Phinius BB, et al. Molecular characterization of near full-length genomes of hepatitis B virus isolated from predominantly HIV infected individuals in Botswana. Genes (Basel). 2018;9(9).
Choga W, Anderson M, Zumbika E, Moyo S, Mbangiwa T, BB P, et al. Molecular characterization of hepatitis B virus in blood donors in Botswana. Virus Genes. 2019;55(1):33–42.
Mabunda N, Zicai AF, Ismael N, Vubil A, Mello F, Blackard JT, et al. Molecular and serological characterization of occult hepatitis b among blood donors in Maputo, Mozambique. Mem Inst Oswaldo Cruz. 2020;115(8):1–7.
Bowyer SM, Van Staden L, Kew MC, Sim JGM. A unique segment of the hepatitis B virus group A genotype identified in isolates from South Africa. J Gen Virol. 1997;78(7):1719–29.
Selabe SG, Song E, Burnett RJ, Mphahlele MJ. Frequent detection of hepatitis B virus variants associated with lamivudine resistance in treated South African patients infected chronically with different HBV genotypes. J Med Virol. 2009;81(6):996–1001.
Makondo E, Bell TG, Kramvis A. Genotyping and Molecular Characterization of Hepatitis B Virus from Human Immunodeficiency Virus-Infected Individuals in Southern Africa. PLoS One. 2012;7(9).
Gededzha MP, Muzeze M, Burnett RJ, Amponsah‐Dacosta E, Mphahlele MJ, Selabe SG. Complete genome analysis of hepatitis B virus in human immunodeficiency virus infected and uninfected South Africans. J Med Virol. 2016;88(9):1560-1566.
Muriel V, Jean-Marc D, Jean-Marie S. Molecular Epidemiology of Hepatitis B Virus in Dakar, Senegal. J Med Virol. 2006;78:329–334.
Candotti D, Opare-Sem O, Rezvan H, Sarkodie F, Allain JP. Molecular and serological characterization of hepatitis B virus in deferred Ghanaian blood donors with and without elevated alanine aminotransferase. J Viral Hepat. 2006;13(11):715–24.
Lawson-Ananissoh L, Attia K, Diallo D, Doffou S, Kissi Y, Bangoura D, et al. Distribution and Clinical Implications of the Genotypes of the Hepatitis B Virus in 33 Chronic Carriers of Hepatitis B Virus in Cote-d’Ivoire. J Afr Hepato Gastroentero. 2017;11(1–5).
Compaore TR, Diarra B, Assih M, Obiri-yeboah D, Soubeiga ST, Ouattara AK, et al. HBV / HIV co-infection and APOBEC3G polymorphisms in a population from Burkina Faso. BMC Infect Dis [Internet]. 2016;1–7. Available from: http://dx.doi.org/10.1186/s12879-016-1672-2
Ahmad A, Bakari A, Priscilla B, Olayinka A. Pattern of Prevalent Hepatitis B Virus Genotypes in Zaria, Nigeria. Niger Postgr Med J. 2019;26(2):80–6.
Boyd A, Maylin S, Moh R, Mahjoub N, Gabillard D, Eholié SP, et al. Hepatitis B surface antigen quantification as a predictor of seroclearance during treatment in HIV-hepatitis B virus coinfected patients from Sub-Saharan Africa. J Gastroenterol Hepatol. 2016;31(3):634–44.
Fujiwara K, Tanaka Y, Orito E, Ohno T, Kato T, Sugihara K, et al. Distribution of HBV genotypes among HBV carriers in Benin: Phyologenetic analysis and virological characteristics of HBV genotype E. World J Gastroenterol. 2005;11(41):6410–5.
Hønge B, Jespersen S, Medina C, Té Dda S, da Silva Z, Lewin S, et al. Bissau HIV cohort study group. Hepatitis B and Delta virus are prevalent but often subclinical co-infections among HIV infected patients in Guinea-Bissau, West Africa: a cross-sectional study. PLoS One. 2014;9(e99971).
Dongdem A, Dzodzomenyo M, Asmah R. Hepatitis B virus genotypes among chronic hepatitis B patients reporting at Korle-Bu teaching hospital, Accra, Ghana. Pan Afr Med J. 2016;25:5.
Huy T, Ishikawa K, Ampofo W, Izumi T, Nakajima A, Ansah J, et al. Characteristics of hepatitis B virus in Ghana: full length genome sequences indicate the endemicity of genotype E in West Africa. J Med Virol. 2006;78:178–84.
Chekaraou MA, Brichler S, Mansour W, Gal F Le, Garba A, Dény P, et al. A novel hepatitis B virus (HBV) subgenotype D (D8) strain, resulting from recombination between genotypes D and E, is circulating in Niger along with HBV/E strains. J Gen Virol. 2010;91(6):1609–20.
Geretti AM, Patel M, Sarfo FS, Chadwick D, Verheyen J, Fraune M, et al. Detection of highly prevalent hepatitis B virus coinfection among HIV-seropositive persons in Ghana. J Clin Microbiol. 2010;48(9):3223–30.
Hübschen JM, Mbah PO, Forbi JC, Otegbayo JA, Olinger CM, Charpentier E, et al. Detection of a new subgenotype of hepatitis B virus genotype A in Cameroon but not in neighbouring Nigeria. Clin Microbiol Infect. 2011;17(1):88–94.
De Paschale M, Ceriani C, Cerulli T, Cagnin D, Cavallari S, Ndayaké J, et al. Prevalence of HBV, HDV, HCV, and HIV infection during pregnancy in northern Benin. J Med Virol. 2014;86:1281–7.
Faleye T, Adewumi M, Ifeorah I, Omoruyi E, Bakarey S, Akere A, et al. Detection of hepatitis B virus isolates with mutations associated with immune escape mutants among pregnant women in Ibadan, southwestern Nigeria. Springerplus. 2015;4(43).
Maylin S, Sire JM, Mbaye PS, Simon F, Sarr A, Evra ML, et al. Short-term spontaneous fluctuations of HBV DNA levels in a Senegalese population with chronic hepatitis B. BMC Infect Dis. 2015;15(1):1.
Traoré F, Gormally E, Villar S, Friesen MD, Groopman JD, Vernet G, et al. Molecular characteristics of Hepatitis B and chronic liver disease in a cohort of HB carriers from Bamako, Mali. BMC Infect Dis. 2015;15(1):1–8.
Ampah KA, Pinho-Nascimento CA, Kerber S, Asare P, De-Graft D, Adu-Nti F, et al. Limited Genetic Diversity of Hepatitis B Virus in the General Population of the Offin River Valley in Ghana. PLoS One. 2016;11(6):1–16.
Candotti D, Diarra B, Bisseye C, Tao I, Pham Quang K, Sanou M, et al. Molecular characterization of hepatitis B virus in blood donors from Burkina Faso: Prevalence of quasi-subgenotype A3, genotype E, and mixed infections. J Med Virol. 2016;88(12):2145–56.
Opaleye OO, Japhet OM, Adewumi OM, Omoruyi EC, Akanbi OA, Oluremi AS, et al. Molecular epidemiology of hepatitis D virus circulating in Southwestern Nigeria. Virol J [Internet]. 2016;13(1):1–8. Available from: http://dx.doi.org/10.1186/s12985-016-0514-6
Boyce CL, Ganova-Raeva L, Archampong TNA, Lartey M, Sagoe KW, Obo-Akwa A, et al. Identification and comparative analysis of hepatitis B virus genotype D/E recombinants in Africa. Virus Genes. 2017;53(4):538–47.
Cella E, Ceccarelli G, Vita S, Lai A, Presti A Lo, Blasi A, et al. First epidemiological and phylogenetic analysis of Hepatitis B virus infection in migrants from Mali. J Med Virol. 2017;89(4):639–46.
Diarra B, Yonli AT, Sorgho PA, Compaore TR, Ouattara AK, Zongo WA, et al. Occult hepatitis B virus infection and associated genotypes among HBsAg-negative subjects in Burkina Faso. Mediterr J Hematol Infect Dis. 2018;10(1):1–9.
Ayodele MBO, Ogugbue CJ, Frank-Peterside N, Tatfeng YM. Prevalent Hepatitis B Virus Genotypes Circulating among HIV Co-Infected Patients in an Urban City, South-South Nigeria. J AIDS Clin Res. 2019;10(1000795):2.
Suzuki S, Sugauchi F, Orito E, Kato H, Usuda S, Siransy L, et al. Distribution of hepatitis B virus (HBV) genotypes among HBV carriers in the Cote d’Ivoire: Complete genome sequence and phylogenetic relatedness of HBV genotype E. J Med Virol. 2003;69(4):459–65.
Forbi JC, Vaughan G, Purdy MA, Campo DS, Xia G liang, Ganova-Raeva LM, et al. Epidemic history and evolutionary dynamics of Hepatitis B virus infection in two remote communities in rural Nigeria. PLoS One. 2010;5(7).
Brah S, Moussa S, Inoua A, Alhousseini DM, Daou M, Madougou B, et al. Molecular characterization of hepatitis B virus from chronically-infected patients in Niamey, Niger. Int J Infect Dis. 2016;45:18–23.
Archampong TN, Boyce CL, Lartey M, Sagoe KW, Obo-Akwa A, Kenu E, et al. HBV genotypes and drug resistance mutations in antiretroviral treatment-naïve and treatment-experienced HBV-HIV co-infected patients. Antivir Ther. 2017;22(1):13.
De Pina-Araujo IIM, Spitz N, Soares CC, Niel C, Lago B V., Gomes SA. Hepatitis B virus genotypes A1, A2 and E in Cape Verde: Unequal distribution through the islands and association with human flows. PLoS One. 2018;13(2):1–16.
Candotti D, Danso K, Allain JP. Maternofetal transmission of hepatitis B virus genotype E in Ghana, west Africa. J Gen Virol. 2007;88(10):2686–95.
Fujiwara K, Tanaka Y, Orito E, Ohno T, Kato T, Sugihara K, et al. Distribution of HBV genotypes among HBV carriers in Benin:phylogenetic analysis and virological characteristics of HBV genotype E. World J Gastroenterol. 2005;11(6410–6415).
Maponga TG, Glashoff RH, Vermeulen H, Robertson B, Burmeister S, Bernon M, et al. Hepatitis B virus-associated hepatocellular carcinoma in South Africa in the era of HIV. BMC Gastroenterol. 2020;1–9.
Henn BM, Gignoux C, Lin AA, Oefner PJ, Shen P, Scozzari R, et al. Y-chromosomal evidence of a pastoralist migration through Tanzania to southern Africa. Proc Natl Acad Sci U S A. 2008;105(31):10693–8.
Rito T, Vieira D, Silva M, Conde-Sousa E, Pereira L, Mellars P, et al. A dispersal of Homo sapiens from southern to eastern Africa immediately preceded the out-of-Africa migration. Sci Rep. 2019;9(1):1–10.
Cookey S. West African Immigrants in the Congo 1885-1896. J Hist Soc Niger. 1965;3(2):261–70.
Castrì L, Tofanelli S, Garagnani P, Bini C, Fosella X, Pelotti S, et al. mtDNA variability in two bantu-speaking populations (shona and hutu) from Eastern Africa: Implications for peopling and migration patterns in sub-Saharan Africa. Am J Phys Anthropol. 2009;140(2):302–11.
Jagganath G, Singh S. ‘Step-wise Migration’: The Case of West African Immigrants in Durban, KwaZulu-Natal, South Africa. African. Renaissance. 2021;18(3):209.
Liu Z, Zhang Y, Xu M, Li X, ZZhang Z. Distribution of hepatitis B virus genotypes and subgenotypes. Medicine (Baltimore). 2021;100(50):27941.
Brown W. White Dominance in South Africa: A Study in Social Control. .. 1939;18:406. Soc F. 1939;18:406–7.
Freund B. South Africa: The end of apartheid & the emergence of the ‘BEE Elite.’ Rev African Polit Econ. 2007;34(114):661–78.
Oyinloye SO, Bukbuk DN. Molecular identification of genotypes of Hepatitis B virus in Borno State, Nigeria. African J Microbiol Res. 2020;15(2):101–6.
UN. United Nations (UN) Country classification: available at https://www.un.org/en/development/desa/policy/wesp/wesp_current/2014wesp_country_classification.pdf. 2014;
Lin C, Kao J. “The clinical implications of hepatitis B virus genotype: recent advances,.” J Gastroenterol Hepatol. 2011;26:123–130.
Lunaček NK, Poljak M, Matičič M. Distribution of hepatitis B virus genotypes in europe and clinical implications: A review. Acta Dermatovenerologica Alpina, Pannonica Adriat. 2018;27(3):141–6.
Kramvis A. The clinical implications of hepatitis B virus genotypes and HBeAg in pediatrics. Rev Med Virol. 2016;26(4):285–303.
Tran T, Trinh T, Abe K. New complex recombinant genotype of hepatitis B virus identified in Vietnam. J Virol. 2008;82:5657–63.
Yu H, Yuan Q, Ge S, Wang H, Zhang Y, Chen Q, et al. Molecular and phylogenetic analyses suggest an additional hepatitis B virus genotype “I”. PLoS One. 2010;5:e9297.
Shi Y. Correlation between hepatitis B virus genotypes and clinical outcomes. Jpn J Infect Dis. 2012;65:476–482.
Velkov S, Ott J, Protzer U, Michler T. The Global Hepatitis B Virus Genotype Distribution Approximated from Available Genotyping Data. Genes (Basel). 2018;9(10):495.
Kafeero H, Ndagire D, Ocama P, Walusansa A, H S. Sero-prevalence of human immunodeficiency virus–hepatitis B virus (HIV–HBV) co-infection among pregnant women attending antenatal care (ANC) in sub-Saharan Africa (SSA) and the associated risk factors: a systematic review and meta-analysis. Virol J. 2020;17(1):19.
Duong T, Horiike N, Michitaka K. Comparison of genotypes C and D of the hepatitis B virus in Japan: a clinical and molecular biological study. J Med Virol. 2004;72:551–557.
Datta S. Molecular epidemiology and clinical significance of hepatitis B virus genotypes, core promoter and precore mutations in eastern India. Intervirology. 2008;51:275–284.
Erhardt A, Blondin D, Hauck K, Sagir A, Kohnle T, Heintges T. Response to interferon alfa is hepatitis B virus genotype dependent: genotype A is more sensitive to interferon than genotype D. Gut. 2005;54:1009–13.
Ming-Whei Y, Shiou-Hwe Y, Pei-Jer C, Yun-Fan L, Chih-Lin L, Chun-Jen L, et al. Hepatitis B Virus Genotype and DNA Level and Hepatocellular Carcinoma: A Prospective Study in Men. J Natl Cancer Inst. 2005;97(4):256–72.
Assih M, Ouattara A, Diarra B, Theophane , AY Compaore T, Obiri-Yeboah D, Djigma F, et al. Genetic diversity of hepatitis viruses in West-African countries from 1996 to 2018. World J Hepatol. 2018;10(11):807–21.
Datta S, Dasgupta D, Ghosh A, Ghosh S, Manna A, Datta S, et al. Oncogenic potential of hepatitis B virus subgenotype D1 surpasses D3: Significance in the development of hepatocellular carcinoma. Carcinogenesis. 2018;39(2):283–92.
Kim H, Lee SA, Kim DW, Lee SH, Kim BJ. Naturally occurring mutations in large surface genes related to occult infection of hepatitis B virus genotype C. PLoS One. 2013;8.
Kafeero HM, Ndagire D, Ocama P, Walusansa A, Sendagire H. Tumor Necrosis Factor-α-863C/A and 1031 T/C single nucleotide polymorphic sites (SNPs) may be putative markers of HBV disease prognosis among Caucasoids: Evidence from a systematic review with meta-analysis. Gene Reports [Internet]. 2022;26(November 2021):101486. Available from: https://doi.org/10.1016/j.genrep.2021.101486
Toan N, Song H, Kremsner P, Duy N, Binh V, Koeberlein B. Impact of Hepatitis B virus Genotypes and Genotype mixtures on the Course of Liver Disease in Vietnam. Hepatology. 2006;43(6):1375–1384.
Mahgoub S, Candotti D, El Ekiaby M, Allain JP. Hepatitis B virus (HBV) infection and recombination between HBV genotypes D and E in asymptomatic blood donors from Khartoum, Sudan. J Clin Microbiol. 2011;49(1):298–306.

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Mapping Hepatitis B Virus Genotypes, Recombinant Genotypes and Sub- genotypes on the African continent from 1997 to 2021: A Systematic Review with Meta-Analysis

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