Saudi Journal of Gastroenterology
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Year : 2006  |  Volume : 12  |  Issue : 3  |  Page : 146-148
Hepatitis B genotyping and its clinical implications

Department of Gastroenterology, Royal Victoria Hospital, McGill University, Ross Pavilion, Room R3, 27, Montreal, QC, H3A1A1, Canada

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Hepatitis B is a crucial medical problem in Saudi Arabia. Different hepatitis B virus genotypes have been discovered and have been shown to cluster in different areas of the world. Hepatitis B virus genotyping has received a lot of attention recently, and its clinical implications are being investigated extensively throughout the world. In this review, we will discuss the virology, epidemiology and clinical implications of the different hepatitis B genotypes.

Keywords: Hepatitis B, genotype, liver disease

How to cite this article:
Aljarallah BM. Hepatitis B genotyping and its clinical implications. Saudi J Gastroenterol 2006;12:146-8

How to cite this URL:
Aljarallah BM. Hepatitis B genotyping and its clinical implications. Saudi J Gastroenterol [serial online] 2006 [cited 2022 Jan 20];12:146-8. Available from:

Hepatitis B virus (HBV) is a common medical problem in Saudi Arabia. HBV genotyping has received a lot of attention recently, and its clinical implications are being investigated extensively throughout the world.

   Virology Top

Different HBV genotypes have been discovered and have been shown to cluster in different areas of the world. HBV genotypes represent naturally occurring strains of the HBV that have evolved over the years in the world. Up to now, seven HBV genotypes have been identified and an eighth one has recently been added.[1],[2] They display an 8% intergroup divergence in the complete nucleotide sequence of HBV and differences in the nucleotide homology of the surface gene, which results in different HBsAg serotypes.

   Epidemiology Top

Genotype A is mainly detected in Northwestern Europe, North America and Africa, whereas genotype B and C are found in the southeastern Asian population. Genotype D is the most common genotype in the Middle East, like Egypt, Yemen, Turkey, Iran and Tunisia. Genotype E and F are seen in East Africa and the New World respectively. Genotype G is a recently determined genotype in France, America and Germany. Genotype H was reported in patients from Central America [Table - 1].

HBV genotypes may contribute to the wide range in prevalence of HBV infection in different parts of the world through differences in rates of replication and ability to evade immune clearance, but studies comparing the replication capacity and immune response of the various HBV genotypes have not been performed. However, many studies have shown a strong relationship between HBV genotypes and mutations in the precore and core promoter regions that abolish or diminish the production of hepatitis B e antigen (HBeAg).[3]

   Clinical implications Top

Hepatitis B genotypes have been correlated with various epidemiological, virological and clinical variables. For example, it has been reported from China that patients with genotype B were younger than those with genotype C and had a lower prevalence of HBeAg.[4] Several other studies reported a correlation between HBV genotype and HBeAg clearance. These studies, all of Asian patients, found that the prevalence of HBeAg was higher in patients with genotype C compared to those with genotype B, suggesting that HBeAg clearance occurred at higher rates among patients with genotype B.[3],[5] Similarly, Sumi et al. conducted a large cross-sectional study involving 585 patients with hepatitis B (258 with chronic liver disease and 74 with HCC) and showed that HBeAg seroconversion rate in patients with chronic liver disease was significantly higher in genotype B patients compared to genotype C.[6]

Correlation between HBV genotypes and clinical outcome of patients with HBV has also been reported. For example, in a study by Kao et al. involving 272 Chinese patients, it was found that patients with genotype C infection have a more aggressive clinical phenotype than those with genotype B infection.[7] In an important Spanish study, 258 patients with hepatitis B were observed for clinical and virological events over a prolonged period of time.[8] They found that sustained biochemical remission and clearance of HBV DNA occurred at a higher rate in genotype A than in genotype D or genotype F. Similarly, the rate of HBsAg clearance was higher in genotype A than genotype D patients. Zeng et al. found a similar result in a recent study from China.[4]

A correlation between HBV genotype and severity of liver disease has also been found in several other studies from Asia. One study found that hepatitis B surface antigen carriers with genotype B had lower histological activity scores.[3] Two other studies involving a total of 490 Chinese patients with chronic HBV infection found that genotype C was more prevalent in patients with cirrhosis.[5],[9] Similarly Chan et al. reviewed liver biopsies from 55 patients with hepatitis B (11 HVB genotype B, 31 from HBV genotype C patients) and found that genotype C was associated with a higher histological activity index compared to genotype B.[10]

The relation between HBV genotype and hepatocellular carcinoma is inconclusive. One study found that genotype B is associated with hepatocellular carcinoma at an earlier age,[9] but this finding was not confirmed by other studies.[5] In Saudi Arabia, where genotype D is most prevalent, according to unpublished data, hepatocellular carcinoma is the second most common cancer in men, the majority of which is associated with hepatitis B, suggesting a strong correlation between HBV genotype D and HCC.

   Response to therapy Top

Preliminary data suggests that HBV genotype B may be associated with a better response to interferon (IFN) antiviral therapy. Wai et al. performed HBV genotyping on stored sera of 109 patients previously enrolled in an IFN randomized controlled trial.[11] Antiviral response was achieved in 39 and 17% of IFN-treated patients and in 10 and 8% of untreated controls with HBV genotype B and C respectively. Multivariate analyses identified HBV genotype B as one of the independent factors associated with antiviral response. Similarly, Kao et al. found that genotype B has a higher response to IFN (41%) compared to genotype C (15%).[7] In another study from Germany involving 64 patients,[12] HBV genotype A had a higher response to IFN compared to genotype D (37 vs. 6%).

In the most recent randomized clinical trials on pegylated interferon,[13] HBeAg loss was significantly higher for genotypes A versus D (47 vs. 25%) and genotypes B versus C (44 vs. 28%).

In contrast to interferon response, studies on HBV genotypes and lamivudine treatment are limited by the small number of patients and heterogeneity in duration of treatment. Thus, no definitive conclusion on correlation between HBV genotypes and response or resistance to lamivudine can be made.[14] The relation between HBV genotype and response to adefovir dipivoxil was studied in 694 patients who participated in the phase III trials.[15] HBV DNA reduction and HBeAg seroconversion occurred in similar proportions of patients with genotypes A-D at the end of 48-week treatment. However, this study combined HBeAg-positive and HBeAg-negative patients and did not provide data on durability of treatment response. In addition, the number of patients with HBeAg seroconversion was too small for a definitive conclusion on the relation between HBV genotype and adefovir-related HBeAg seroconversion.

   Conclusion Top

HBV genotyping is emerging as a useful additional laboratory test that may add additional information that may affect epidemiological factors, clinical outcome and response to therapy.

   References Top

1.Norder H, Courouce AM, Magnius LO. Complete genomes, phylogenetic relatedness and structural proteins of six strains of the hepatitis B virus, four of which represent two new genotypes. Virology 1994;198:489-503.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Naito H, Hayashi S, Abe K. Rapid and specific genotyping system for hepatitis B virus corresponding to six major genotypes by PCR using type-specific primers. J Clin Microbiol 2001;39:362-4.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]
3.Lindh M, Hannoun C, Dhillon AP, Norkrans G, Horal P. Core promoter mutations and genotypes in relation to viral replication and liver damage in East Asian hepatitis B virus carriers. J Infect Dis 1999;179:775-82.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]
4.Zeng G, Wang Z, Wen S, Jiang J, Wang L, Cheng J, et al . Geographic distribution, virologic and clinical characteristics of hepatitis B virus genotypes in China. J Viral Hepat 2005;12:609-17.  Back to cited text no. 4    
5.Ding X, Mizokami M, Yao G, Xu B, Orito E, Ueda R, et al . Hepatitis B virus genotype distribution among chronic hepatitis B virus carriers in Shanghai, China. Intervirology 2001;44:43-7.  Back to cited text no. 5    
6.Sumi H, Yokosuka O, Seki N, Arai M, Imazeki F, Kurihara T, et al . Influence of hepatitis B virus genotypes on the progression of chronic type B liver disease. Hepatology 2003;37:19-26.  Back to cited text no. 6    
7.Kao JH, Wu NH, Chen PJ, Lai MY, Chen DS. Hepatitis B genotypes and the response to interferon therapy. J Hepatol 2000;33:998-1002.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]
8.Sanchez-Tapias JM, Costa J, Mas A, Bruguera M, Rodes J. Influence of hepatitis B virus genotype on the long-term outcome of chronic hepatitis B in western patients. Gastroenterology 2002;123: 1848-56.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.Kao JH, Chen PJ, Lai MY, Chen DS. Hepatitis B genotypes correlate with clinical outcomes in patients with chronic hepatitis B. Gastroenterology 2000;118:554-9.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]
10.Chan HL, Tsang SW, Liew CT, Tse CH, Wong ML, Ching JY, et al . Viral genotype and hepatitis B virus DNA levels are correlated with histological liver damage in HBeAg-negative chronic hepatitis B virus infection. Am J Gastroenterol 2002;97:406-12.  Back to cited text no. 10    
11.Wai CT, Chu CJ, Hussain M, Lok AS. HBV genotype B is associated with better response to interferon therapy in HBeAg(+) chronic hepatitis than genotype C. Hepatology 2002;36:1425-30.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]
12.Erhardt A, Heineke U, Blondin D, Gerlich W, Adams O, Heintges T, et al . Mutations of the core promotor and response to interferon treatment in chronic replicative hepatitis B. Hepatology 2000;31:716-725.  Back to cited text no. 12    
13.Janssen HL, van Zonneveld M, Senturk H, Zeuzem S, Akarca US, Cakaloglu Y, et al . Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: A randomized trial. Lancet 2005;365:123-9.  Back to cited text no. 13    
14.Kao JH, Liu CJ, Chen DS. Hepatitis B viral genotypes and lamivudine resistance. J Hepatol 2002;36:303-4.  Back to cited text no. 14    
15.Westland C, Delaney W 4th, Yang H, Chen SS, Marcellin P, Hadziyannis S, et al . Hepatitis B virus genotypes and virologic response in 694 patients in phase III studies of adefovir dipivoxil. Gastroenterology 2003;125:107-16.  Back to cited text no. 15    

Correspondence Address:
Badr M Aljarallah
Department of Gastroenterology, Royal Victoria Hospital, McGill University, Ross Pavilion, Room R3, 27, Montreal, QC, H3A1A1
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-3767.29757

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[Table - 1]

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