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Short Communication

Horizontal transmission of hepatitis B

virus in Turkey

H. Deg

˘ertekin

*

, G. Gu

¨nes

x

Ufuk University, School of Medicine, Ankara, Turkey

Received 28 April 2007; received in revised form 13 November 2007; accepted 14 April 2008 Available online 26 August 2008

Worldwide, there is a close relationship be-tween endemic frequency and the route of trans-mission of hepatitis B virus (HBV) infection. Parenteral and sexual transmission is seen in low endemic Western populations, while vertical trans-mission is the main route in Far East and African countries. Horizontal transmission is accepted as the most common route in Middle Eastern and Mediterranean countries.1

Vertical transmission occurs through the umbil-ical cord in the intra-uterine period, during labour or postnatally in the first 6 months of life. Beyond 6 months of age, during childhood, adolescence (10e19 years) and young adulthood (15e24 years), transmission of HBV via routes other then paren-teral or sexual is termed ‘horizontal’.

The mechanism of horizontal transmission is not yet clear. It may occur via frequent or long-term contact of non-intact skin or mucous membranes with blood-stained secretions or saliva. Experi-mental data have shown that Hepatitis B surface antigen (HBsAg)-positive saliva is not infectious if swallowed, but transmission does occur when it is injected subcutaneously or if it reaches the circu-lation via a human bite.2

Transmission between close contacts such as mother and child, siblings and close friends has

been shown to occur following small skin cuts, bites, dermabrasion or sharing toys and tools.1

Vertical and horizontal transmission of HBV have been studied widely in countries with high seropositivity. The HBV carrier rate is high (>10%) in endemic countries in the Far East and Africa. In these parts of the world, 20e40% of mothers are HBsAg positive, particularly Hepatitis B e antigen (HBeAg) positive. More than 50% of young people aged 10e20 years are Hepatitis B surface antibody (anti-HBs) positive, while this figure is nearly 70% in the general population. Not surprisingly, the rate of hepa-tocellular carcinoma (HCC) among children and young adults is very high.1,3

It is well known that HBV infection has a higher tendency to become chronic when transmitted vertically. As such, 90% of babies born to HBeAg-positive mothers develop chronic HBV infection.1

Despite HBV endemicity in Africa and high HBeAg positivity among pregnant women (>20%), vertical transmission is rare. Even when mothers are HBeAg positive, infants are usually HBsAg negative for the first 6 months to 1 year of life; in Senegal, positive serology occurs beyond 3 years of age. Horizontal transmission is therefore the main route.1,3

These data suggest differences in vertical and horizontal transmission among geographic regions and populations in the world. The most probable explanation is differences in genotype. HBV

* Corresponding author. Tel./fax:þ90 312 439 0806. E-mail address:hdegertekin@hotmail.com(H. Deg˘ertekin).

0033-3506/$ - see front matterª 2008 The Royal Institute of Public Health. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.puhe.2008.04.010

Public Health (2008) 122, 1315e1317

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genotypes B and C are known to be common in the Far East, while genotypes A and E are more common in Africa. In addition, precore and preS gene mutations in HBV have been shown to be related to horizontal transmission of the virus.1,3

Turkey has intermediate endemicity for HBV. The HBsAg carrier rate is 4% (2e8%), while anti-HBs positivity is 30% (20e55%). On average, 40% (30e 70%) of patients with chronic liver disease are HBsAg positive. These figures are lower in Western Turkey, and much higher in East and South-east Turkey where socio-economic levels are lower.4,5 Numerous studies have investigated HBV seroposi-tivity in Turkey in various age groups, pregnant women, newborns and young adults.4,5

The aim of this article is to summarize and comment on studies in Turkey regarding HBV transmission. In this cross-sectional study, data were collected retrospectively from material pub-lished in medical journals and abstract books.

The data supporting horizontal transmission as the main route in Turkey are outlined below.

 HBV carrier prevalence in Turkey shows inter-mediate endemicity (4%). This resembles Med-iterranean and Middle Eastern countries. In these countries, especially in Spain, Italy and Greece, HBV is transmitted horizontally and the carrier rate has decreased significantly in the last two decades with improvements in socio-economic conditions and a decrease in the number of crowded families.6,7

 In Turkey, HBsAg positivity is not significantly higher in pregnant women (average 4.4%,

Table 1), and HBeAg positivity is also very low (average 7%). This lowers the risk of vertical transmission from mothers to newborn babies.

 Newborn and childhood populations in Turkey are reported to have lower HBV seropositivity compared with highly endemic countries. Ap-proximately 4% of children in Turkey are HBsAg positive and approximately 15% are anti-HBs positive (Table 1). In countries where vertical transmission is the primary route, approxi-mately 20% of children are HBsAg positive and approximately 50% are anti-HBs positive; these differences are significant.

 In Turkey, studies have demonstrated that HBV seropositivity tends to increase gradually fol-lowing the newborn period, and peaks between 5 and 15 years of age.

 Studies comparing vertical and horizontal routes of transmission have yielded valuable results. Maternal seropositivity, high number of siblings and a small age difference between siblings have been demonstrated to be posi-tively correlated with intrafamilial transmis-sion of HBsAg.8,9

 In contrast to countries in the Far East where vertical transmission is dominant, the preva-lence of HCC is significantly lower among chil-dren in Turkey.

 HBV-related chronic liver disease is generally seen at earlier ages in high-risk regions, and seen in the elderly in low-risk countries. In Turkey, affected individuals are mainly middle aged.  Similar to neighbouring countries, HBV

geno-type D is the most common genogeno-type in Turkey. Horizontal transmission was strongly supported by a regional study in South-eastern Turkey (Diyar-bakir). The study was conducted among elementary and middle school students. The results demon-strated that 2.4% of first graders were HBsAg positive, and this increased to 5.8% in fifth graders and 6.7% in eleventh graders.10These figures corre-late with the HBsAg positivity rate of 9% in adults in the region. Similarly, anti-HBs positivity increased from 14% to 29% and 21% in the same population of first, fifth and eleventh graders, respectively. These figures explain the high prevalence in Turkish chil-dren aged 7e12 years.

Two studies have reported strongly in favour of horizontal transmission.8,9The results can be sum-marized as follows.

 The presence of an HBsAg-positive family mem-ber increases the risk of transmission by at least two fold.

 In families with more than five members and the children of these families, HBsAg positivity is ap-proximately 26.3% and 33.6%, respectively, compared with 18.9% in families with fewer

Table 1 Prevalence of hepatitis B virus in Turkey compared with countries where vertical transmission is the main route

Group Countries with vertical transmission

Turkey

HBsAg carrier >10% 2e10%

Anti-HBs (þ) 70% 30e50%

Pregnant HbsAg (þ) 50% 4% Pregnant HBeAg 20% 7% Children HBsAg 20% 4% Children anti-HBs 50% 15% Children HCC Frequent Very rare Chronic liver disease Young adults Middle aged

adults HBV genotype A and E D

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than five members and 17.5% among the children in these smaller families (P < 0.01).

 If the age difference between siblings is less than 3 years, HBsAg positivity is approximately 66%, compared with 26% when the age difference be-tween siblings is more than 3 years (P < 0.01).  If both the mother and father are HBsAg

nega-tive, the risk in their children is 8%; in compar-ison, the risk is as high as 28% when both parents are carriers. The highest risk occurs when both parents are seropositive, followed by the mother alone and then the father alone. The lowest risk is when both parents are seronegative.

 For children up to 4 years of age, there is no correlation between child and maternal serol-ogy; however, maternal status becomes impor-tant beyond 4 years of age. This can be explained by the increased daily activity of the child, leading to simple scratches and trauma, as well as circumcision and ear pierc-ing. Children are usually under their mother’s supervision, and she is usually the primary carer after accidents and circumcision.  HBV seropositivity peaks between 5 and 15

years of age.

 A mother with chronic HBV infection increases the risk of transmission to her children by five fold, while this risk is 10 fold for her partner. In conclusion, Turkey demonstrates intermedi-ate HBV endemicity, similar to Mediterranean countries where horizontal transmission is the primary route. Vertical transmission is probably lower due to lower prevalence of HBsAg, especially HBeAg, among pregnant women. The HBV geno-type is also a possible factor. HBV transmission in the family occurs beyond 4 years of age between mother and child or between siblings. The risk of transmission continues during the school years and increases until 15 years of age. HBV transmission mainly occurs in childhood and adolescence. The demographic profile of chronic liver disease in Turkey supports this conclusion. The present situ-ation in Turkey has similarities with the situsitu-ation in other Mediterranean countries, like Spain and Italy, two decades ago. The present data underline once more the importance of widespread HBV

vaccination in newborns, children and adoles-cents, and informing families about HBV trans-mission routes.

Ethical approval

None sought.

Funding

None declared.

Competing interests

None declared.

References

1. Lavanchy D. Hepatitis B and other Hepadnaviridea. Epide-miology. Chapter 11. In: Thomas HC, Lemon S, Znekeno AS, editors. Viral hepatitis 3rd ed.; Blackwell Pub-lishing; 2005. pp. 181e92.

2. Hui AY, Hung LCT, Tse PCH, Leung W-K, Chan PKS, Chan HLY. Transmission of hepatitis B by human bite e confirmation by detection of virus in saliva and full genome sequencing. J Clin Virol 2005;33:254e6.

3.http://www.who.int/csr/disease/hepatitis/whocdscsrlyo 20022/en/index1.html.

4. Degertekin H. The main transmission route of HBV infection is horizontal. Hepatitis B Update Meeting, 9e11 January 2007, Turkish Association of Study for Liver Disease, _Istanbul. pp. 19e27.

5. Mıstık R. The epidemiology of viral hepatitis in Turkey. Anal-ysis of published data. In: Tabak F, Balık _I, Tekeli E, editors. Viral hepatitis. Ankara: Association of Viral Hepatitis; 2007. p. 10e50.

6. Zampino R, Lobello S, Chiaramonte M, Pasini CV, Dumpis U, Thursz M, et al. Intrafamilial transmission of hepatitis B virus in Italy; phylogenetic sequence analysis and aminoacid variations of the core gene. J Hepatol 2002;36:248e53.

7. Zervou EK, Gatselis NK, Xanthi F, Ziciadis K, Georgiadou P, Dalekos GN. Intrafamilial spread of hepatitis B virus infection in Greece. J Pediatr Gastroenterol Nutr 1993;17:346e7. 8. Kandemir O¨, Kaya A, Kanık A, Sxahin E. Intrafamilial

trans-mission of HBV. Turk J Viral Hepatitis 2002;1:459e62. 9. Karago¨z K, Felek S, Kalkan A, Akbulut A, Kılıc¸ SS. Horizontal

transmission of HBV. Turk J Viral Hepatitis 1997;2:100e5. 10. Deg˘ertekin H, Tuzcu A, Yalcxin K. Horizontal transmission of

HBV infection among students in Turkey. Public Health 2000;114:411e2.

Available online at www.sciencedirect.com

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