hepatitis b virus is one of the most important factors for infected diseases in the world .
it was estimated that 350 million people infected with hepatitis b virus and almost 75% patients are living in asia ( 1 ) .
nearly one million people die annually from chronic liver diseases such as , chronic hepatitis b , cirrhosis and hepatocellular carcinoma ( 2 ) .
the prevalence of hepatitis b is reported various in different parts of the world , so this virus existed as hyper endemic in most asian countries . throughout the world , carrier variability rate for hepatitis b infection is estimated to be 0.1% to 20% which is different in various areas and is classified into three regions : the first group with areas as having low ( < 2% ) , the second group with intermediate prevalence ( 2 - 7% ) and with high prevalence ( > 8% ) ( 3 ) .
the prevalence of hepatitis b infection is high in africa , southeast asia , the middle east , southern and western pacific island , ( they are of endemic regions ) intermediate areas consist of south central and southwest asia , israel , japan , eastern , southern europe and russia and prevalence of hepatitis b infection is low in northern and western europe , north america , australia , new zealand , mexico and southern america ( 4 ) . in iran , a study showed that 35% of population were infected with hepatitis b and the percentage of chronic carriers is about 3% ; although after implementing control programs and public vaccination , the prevalence of hbv infection has reduced to less than 2 % ( 5 ) .
the hbv has ten genotypes ( a - j ) , multiple subtypes and serotypes ( adr , adw , ayr , ayw ) , showing genotypes vary in different geographic areas worldwide . there is a relation between serotype and genotype in the world ( 6 ) .
it seems that infected persons with different genotypes show various responses to therapy ( 7 ) . also different in genotypes
have shown influences in sever course of disease , infection and vaccination ( 8) . some studies suggested that genotype d could increase the risk of cirrhosis than genotype c(9 ) , on the other hand some evidences showed no difference between these types in infection risk to hcc(10 ) .
moreover some researches found that genotype a is more associated with higher risk of hcc than genotype d(11 ) .
recent study showed that genotype c was more strongly associated with hcc than infected patients with genotypes a , b and d ( 12 ) .
pre - core stop codon and basal core promoter mutations are of another difference in risk of hcc in various hbv genotypes .
pre - core stop codon a1896 is less in genotype c than genotype b. basal core promoter mutations in x gene upstream of pre - core area is more in genotypes c ( 13 ) .
this mutation increases the risk of hcc in patients with chronic hepatitis ( 14 ) .
hbv genotypes have different distinguished biological and are able to influence the expression of antigen and immune functional , so recognizing hbv genotypes is important in a country .
this article has investigated the hbv genotyping and was carried out iran based on papers that identified hbv genotype in iranian population published in english and persian languages .
this genome of hbv includes circular dna that some part of it is bi - string and contains reverse transaction enzyme and/or polymerase dna full string genome contains 3020 - 3320 nucleotides and short length strand is 1700 - 2800 nucleotides
. there are four areas encoded by hbv genome c , x , p , s .
some mutants have found in hepatitis b. in many of this , mutation in pre - core genome is associated with inactivation of hbe ag ( ymdd , s mutant ) ( 15 ) . in patients ,
this mutant is associated with severity of disease and less response to therapy ( 16 ) .
ymdd region in virus polymerase is located in places influenced by most of reverse transcriptase inhibitor such as lamivudine and lamivudine .
variation of ymdd occurred as a result using lamivudinethus , after one year therapy with lamivudine , nearly 24% of patients have showed ymdd mutations ( 17 ) .
many of pre - core mutations are related to g - a changing in the 1896 nucleotide , causing the stop codon and preventing the functional of hbe ag genome . a study has reported that 58% of infections are the type of pre - core infection in iran(19 ) .
negative hbe ag carriers have been heterogeneous ; most of them have had less dna level and normal alanintransferase ; so they could not be able to completely respond to therapy .
some evidences showed that 15 - 20 of hbe ag carriers have a high level of alt and hbv dna in mediterranean , eastern asia and southern europe ( 20 ) .
genotype a is divided into two sub - genotypes aa ( a1 ) , ae(a2 ) .
sub - genotype aa ( a1 ) was found in africa / asia and philippine .
genotype b is also divided into two sub genotype ba / b2 ( asia ) and bj / b2 ( j - japan ) and the prevalence of them has been reported in different areas .
ba has classified to four classb2-b4 , these sub genotypes have more virulence than bj ( 21 ) .
cs ( c1 ) is more common in south east of asia and ce ( c2 ) was observed in japan , china , korea , east of asia ( 22).c3 was reported in polynesia , caledonia areas and c4 was detected in australia , and c5 and c6 were found in philippine ( 23 ) .
genotype c , is associated with hepatocellular carcinoma in japanese patients and it was not found in taiwanese patients less than 50 years of age ( 24 ) .
genotype d is divided into seven sub - genotype ( d1-d2 ) which are prevalent in pakistan , india , afghanistan , mediterranean areas ( 26 ) .
studies show that sub genotypes d1and d2 were found in turkey ( 27 ) but sub genotype d3 was observed more in asia ( east india ) , south of africa and europe and sub genotype d4 was identified in australia ( 28 ) .
recently sub genotype d5 has been reported in east of india and japan ( 29 ) .
a study suggested that genotype d and serotype ayw2 with 94/4% are predominant in hbv positive in iran ( 30 ) .
genotype f has been divided into four sub genotype ( f1-f4 ) , also sub genotype f1 was classified to two sub genotype 1a , 1b .
sub- genotypes f2 , f1 were observed in venezuela and sub genotype f3 was found in east and west of america .
some evidences showed that sub genotype 1a from f1 is derived from center of america , sub genotype f3 is found in north of america and sub genotype f4 had been identified from south of america , but sub genotypes of 1b from f2 is prevalent in most of united states instead of north of southern america and north of america ( 31 ) .
genotype f is predominant in brazil and genotype g is reported in france and united state ; also 4 - 8 % difference in subtypes of genotype e and f has been reported ( 32).genotype h is limited to center of america , mexico and california(33 ) .
it has been reported that genotype i was found in north east of india and genotype j was detected in japanese patients ( 33 ) .
epidemiology of hbv genotypes in the world ( 34 ) there are some significant differences in clinical characteristics and virology of infected patients with various genotypes .
in this study we found 22 studies that were discussed about serotypes and genotypes of hbv in iran . in six studies ,
serotype ayw2 was reported as the predominant serotype with relatively abundance more than 94% ( table 1 ) .
the first study about genotypes of hbv was done in 2005 in iran and genotype d is defined as predominant genotype in iran ( table 2 ) .
in this article , 22 studies were discussed about serotypes and genotypes of hbv in iran .
the results of these studies indicate that the predominant genotype and serotype in iran is d and ayw2 , respectively .
in other studies , there is genotype d in south asia and east asia , such as iran , afghanistan and india ( 57 ) .
this genotype was found the oldest type widely spread in the world . also , addition to ancient civilization , evolving a special genotype for hbv shows its evolution .
in addition , the importance of geographical distribution by presenting genotype d has been reported 46  % in the areas surrounding iran such as pakistan , north india ( 58 ) .
in the south of japan ( okinawa ) it was indicated that genotype b is the predominant genotype ( 59 ) while in mainland genotype c is predominant ( 60 ) .
this relations show that factors for the area of human and racial populations are more important than the geographical factors . in asian countries such as india genotype d and sub - genotype d3
genetically research dna mitochondria chromosome y in indians showed the integration of migrators ' genotypes from europe countries that defines in the northern area more than india ( 62 ) .
other studies have showed that abundance of genotype hbv can be the reflection of geographical close relation among this transformation .
genotype d is the oldest type that has spread widely in the world ( nicobar and andaman islands ) .
also , there are genotypes a and d in the north of india and much more probably it is due to migration from europe which resulted in high prevalence of genotype d in most parts of india . in iran , it can be deduced that aryans was first habitants of caspian sea , then migrated to the other areas of india and europe .
it is possible that some persons infected with genotype d were infected before migration and caused to spread it .
therefore , in iran , india and most of europian countries , genotype d is seemingly prevalent ( 63 ) . besides the old civilization ;
genotype b is predominant in southern japan ( okinawa ) ( 64 ) ; while genotype c has been reported as the dominant type in mainland japan ( 65 ) . in various areas of japan
genetic studies of mitochondrial dna and y chromosome in indian population indicates the integration of immigrants gene from european countries and in northern parts is more than of south india(67 ) .
another study showing the prevalence of hbv genotype and changing geographical ; so that genotype d is more prevalent in west india . that genotypes a and d are in the north of india ,
is likely related to the migration of people from europe to india and led to genotype d is replaced by genotype a in main areas . in iran , we can know that the aryans have been in the north caspian sea , and then they moved to other parts of iran , india and europe .
it seems that genotype d patients have been infected with virus before migration , and then they led to increasing this genotype so genotype d is prevalent in iran , india and most of europe ( 68 ) .
because hbv genotypes show distinct geographical distribution , genotype d is predominant in iran . despite the different geographical areas in different parts of iran , genotype d is considered as the predominant genotype . with regard to surveillance , hepatitis in iranian health system , defining sequences among different isolates of hbv by appropriate intervals or disease outbreaks
also , knowing infection to hbv genotypes can help in the standardization of treatment interference and selection of proper regimens for this disease .
 hepatitis b virus ( hbv ) infection is a public health problem as a cause of liver diseases including hepatocellular carcinoma and cirrhosis . 
 it is estimated that 350 million people live with chronic infection and about one million people die every year from complication of this chronic disease in the world . 
 so far , ten hbv genotypes ( a - j ) has been identified which show a geographical distribution . throughout the world , carrier variability rate for hepatitis b infection is estimated to be 0.1% to 20% , with regions classified as having low endemicity ( < 2% ) , intermediate endemicity ( 2 - 7% ) and high endemicity ( > 8% ) . 
 the prevalence of hepatitis b infection is estimated at 2 to 7 percent in iran . 
 after hbv vaccination program the prevalence of hepatitis b infection has been reported less than 2% , so iran can be considered one of the countries with low hbv infection endemicity . in iran several studies 
 were shown that the only genotype of hbv(100%)was found genotype d as the prominent type in some provinces , but some studies reported genotype b(5%)as well as genotype d(95%).the distribution of hbv genotypes may guide us in determining disease burden , prognosis and antiviral responses . 
 so , it is important to know the epidemiologically of hbv genotyping as well . 
1. INTRODUCTION
2. HBV MUTANTS
3. GEOGRAPHICAL PREVALENCE HBV GENOTYPES IN THE WORLD
4. EPIDEMIOLOGY OF SEROTYPES AND GENOTYPES OF HBV IN IRAN
5. DISCUSSION
6. CONCLUSION