Age- and region-specific prevalence estimates
The age- and region-specific analysis relied primarily on community-based studies from various regions. The results yielded a marked difference in the overall region-specific estimated prevalence, which ranged from 3.52 to 6.76. The age-specific prevalence also varied greatly between the lowest prevalence in the age group of 0-14 years (2.84) and the highest prevalence, age group 25-34 years (6.36). The overall country-specific prevalence was 4.57, retrieved from the meta-analysis, across all regions and age groups.
Region-specific, HBsAg-prevalence estimates for different sample populations
Population sample groups such as blood donors have been used as a convenient means to estimate the country-specific prevalence of HBV . Since blood donation in Turkey is voluntary and the predonation eligibility assessment is quite strict, a healthy donor effect prevails in this sample population, and likely leads to an underestimation of the true HBV prevalence. Blood donors in this case cannot be representative of an entire population. Our results showed a difference in the region-specific estimates, where the weighted mean prevalence (WMP) ranges from 2.53 to 4.25. When compared with the age- and region-specific outcomes, the results in this sample population are in the low range, whereas the results in the hospital-setting studies are in the high range. Thus, results based on blood donors and from hospital settings should be interpreted with caution.
Another convenient sample of population-based studies is the military conscripts. Military service prevalence studies provide good estimates for the general population of men between the ages of 17 and 41, while pregnant women studies represent the comparable female population of the same age range. Both these sample groups are more representative than blood donors and those from hospital settings. Although screening for HBV in pregnant women is not yet routine in Turkey, nonetheless pregnant women are likely to be tested during their pregnancies, either for research or for health purposes. Our WMP results comparing these 2 groups suggest that HBV is more prevalent among males.
Strengths and limitations
The main strength of this systematic review is that it includes all available Turkish studies, including both published and unpublished abstracts (grey literature), to overcome publication bias, and in particular language bias. Due to the paucity of studies from Turkey on hepatitis B in English, this review provides a wealth of information that would not be accessible to scientists and policy makers from other countries in the world. We used an innovative approach to fit generalized linear mixed models in estimating the prevalence from various studies. Including the year of the study as a linear term in the model showed no significant trend in prevalence over time. Since prevalence is assumed to be not constant, this could be a limitation of the model. Another limitation may be the dependence on the quality of the original reports. The strength of the study may also be a weakness in that conventional wisdom points towards an inverse correlation between quantity and quality. Despite this limitation, we believe that the study provides useful data on the epidemiology of hepatitis B in Turkey for health planning strategies, both in Turkey as well as in the Turkish migrant population. We suggest that researchers who are preparing observational research, such as sero-survey studies, implement the STROBE guidelines  to ensure a clear presentation of what was planned, done, and found in such a study.
Comparing the eras of pre-vaccination and post-vaccination
Since the implementation of universal vaccination in 1998 of all children and risk groups, a decline in prevalence has been observed . Although the current study does not address this issue directly, the availability of age-specific prevalence rates in the postvaccination era enables us to make meaningful comparisons in children from studies in the prevaccination era. In this context, Kanra et al.  studied the prevalence in all regions of Turkey among children before the vaccination policy was implemented. Their finding of an overall country prevalence of 5.90 among 0-15-year-olds compares favourably to the current overall country prevalence rate of 2.84 reported in this study for the same age group. The impact of vaccination was also assessed in health care workers and health care students. The WMP estimates in the postvaccination studies show a decline, which could be explained by the impact of the vaccination campaign or, as a secondary explanation, that HBV has the tendency to decrease over the years. A study from the United States shows patterns in the success of vaccination application to health care workers .
Implications for health policy
Nearly every country with a large or diverse geographic area is expected to have regional differences in HBV prevalence, and the extent of the geographic variation can be very important. The large regional differences in prevalence in Turkey are mainly due to differences in socioeconomic status, lifestyles, infrastructure, and access to health services. In the eastern and south-eastern regions (treated as 1 region) of Turkey, all reasons mentioned above apply in a negative way, though the latest years have witnessed much improvement in the socioeconomic, and hygienic and sanitary conditions in this region and in Turkey in general. This region also lags behind in coverage of HBV vaccination. Although only 18% of the total population live in this area, the estimated number of CHB cases is almost equal to that of the other regions, which have higher population numbers (see Figure 1). A substantial migration has taken place from the southeast and east to the west of the country, mainly for economic reasons. The scarcity of reports from southeast and east Turkey, despite the magnitude of the CHB problem, may be an indirect reflection of the health infrastructure of this region. The region-specific data in this study could stimulate a broad-based prevention and control campaign whereby hepatitis B vaccines and/or treatment and monitoring could be targeted to high-priority regions. Turkey has a large proportion of young people (age 14-30 years, which is more than 66% of the total population). It is a dynamic society with a growing number of educated people; further, the proportion of the population living in cities has increased dramatically in recent decades and now accounts for approximately 70% of the national total. With an average prevalence of 3.50 in young people age 0-24 years, hepatitis B remains a significant public health problem in Turkey.
Another important facet of the data in this study is linked to disease awareness, although this is certainly not specific to Turkey, since CHB patients in general are mostly asymptomatic. With an overall HBV prevalence of 4.57, the estimated number of HBV carriers in Turkey is 3.3 million. Even a very conservative assessment means that 10% of the carriers would need treatment, yielding 330,000 chronic HBV cases eligible for treatment in Turkey alone. We recently estimated that treatment of CHB patients with active disease with a low-resistance profile drug could reduce mortality related to liver disease in this group by 80% . It needs to be stressed that in Turkey, viral hepatitis treatment is fully reimbursed through the national insurance system. According to net sold medication counts per year, it was calculated that no more than 10% of eligible patients receive active treatment , indicating a massive shortcoming in ensuring prolonged life and even life-saving treatments. Chronic HBV infection is a lifelong illness. It can cause serious, life-threatening complications, such as cirrhosis, liver cancer, or liver failure. Most liver transplants in Turkey are attributed to liver disease from chronic HBV. A viral hepatitis national plan should be designed that will lower hepatitis prevalence, increase research, and accelerate access to care for the chronically infected. Testing for immunization coverage should be instituted at the state and regional level. Potential next steps would be to improve epidemiologic surveillance systems, develop a hepatitis registry, and implement serosurveys in order to produce reliable data to guide prevention and control measures and to monitor the impact of preventive strategies.
The importance of our study is certainly not confined to the borders of Turkey. Recent evidence suggests that the overall decline in HBV prevalence in the last decade in industrialized countries of Europe appears to have reached a plateau. The most likely reason why the progressive decline in HBV prevalence has come to a halt is migration from endemic areas [96, 97]. There are currently more than 3 million immigrants, descendants of immigrants, and naturalized citizens and political refugees from Turkey in Western Europe, representing the largest immigrant group in the European Union. The public health implications of the current study thus go far beyond the border of Turkey.