Prevention of viral hepatitis in Greece: Lessons learnt and the way forward. (2007).

Meeting conclusions

The Viral Hepatitis Prevention Board held its autumn meeting  November 15-16, 2007 in Athens, Greece. The objectives of the meeting were to provide an overview of viral hepatitis in Greece.
This section provides highlights of meeting sessions and is concluded with lessons learnt and recommendations for future actions.

Organization of health care (HC) system in Greece
• The Greek HC system is a complex mixed system, with health services organized in 3 sectors including the NHS (mainly funded by state taxes), Social Insurance Services (funded by social insurances) and the private Sector.
• Primary HC centers are developed mostly in rural areas, as part of NHS, while in urban areas, IKA- funded services and the private sector – with a high number of private doctors and diagnostic centers – are mainly used.
• 44% of hospitals are public, large capacity, structures while 54% are private smaller entities; 69% of hospital beds belong to the public sector and 28% to the private sector, Greece meets the WHO requirement for beds/population ratio.
• The ratio of public/private health expenditure in Greece has evolved to approximately 50/50, with public expenditure mainly devoted to hospitals and private expenditure mainly spent on primary HC. Greece has the lowest level of public health expenditure in Europe, leading to:

• social inequities in the access to health services
• fragmented responsibilities between ministries and related lack of organized prevention health promotion
• inadequate management of HC resources
• poorly regulated private sector.

Viral hepatitis surveillance, prevention and control in Greece
• Viral hepatitis surveillance conducted by the HCDCP in Greece aims at disease identification, monitoring and prevention. Within the HCDCP, the Office of Viral Hepatitis works in collaboration with a Scientific Commission of Viral Hepatitis whose objectives consist in prevention, education, surveillance, improvement of medical care and coordination of the nationwide HepNet.Greece study.
• The current ID surveillance programme is based on a mandatory weekly notification system for selected diseases, based on EU case definition and standardized notification form, and is compliant with the EU decisions relating to surveillance. Notification is mainly done by hospitals but considerable non-compliance from physicians leads to major underreporting. Introduction of a separate laboratory notification system for viral hepatitis infections (asymptomatic versus symptomatic) might be considered in order to improve
current surveillance of viral hepatitis in Greece and to reduce underreporting by private physicians.
• Awareness and recognition of the limitations of existing surveillance data have led to initiatives such as the design and conduct of
additional epidemiological studies, as well as issuing and updating guidance and recommendations by the HCDCP.
• Different approaches to study national seroprevalence were presented and discussed to document age-specific prevalence at national level, burden of disease and impact of prevention interventions, including:

•Prediction model through back calculation methods, based on current data
•Seroprevalence study based on residual samples (ESEN-like)
•Population-based serosurvey
•National health survey.

• HCDCP is responsible for the coordination of HepNet.Greece, a large nationwide retrospective-prospective study that started in 2003 and involves chronic HBV and HCV patients. The primary objective is to investigate the course and outcome of chronic HBV, HDV and HCV. Secondary targets are to obtain an indirect estimate of the incidence of chronic HBV, HDV and HCV infection from the yearly number of newly diagnosed patients; to achieve early diagnosis through better screening and surveillance; to introduce common standards of care and more effective treatment of HBV and HCV patients; and to improve collaboration between Hepatology
Centers in Greece. This ongoing Hepnet.Greece study provides opportunities for planned research.

Experience from surveillance of infectious diseases during the 2004 Olympics
Enhanced surveillance systems (in particular, daily reporting) and new syndromic surveillance system were implemented during the 2004 Olympics in Greece. New SOPs for data interpretation were developed and significant expertise was built among HCDCP staff.

Surveillance in blood bank
Implementation of ÍÁÔ technology in individual blood donations, in addition to serological screening, reinforces the safety of blood supply, supporting the value of establishing NAT as a routine screening test which is particularly relevant for the detection of occult blood infection (OBI) cases missed by HBsAg screening. However, the clinical significance of OBI and the impact on donor management should be further studied in order to fully assess the benefit of NAT-testing in terms of reduced morbidity and mortality.

Epidemiology of HAV in Greece
• No reliable national data on HAV disease burden are available: results are only available from small studies with high variability and significant underreporting is anticipated.
• Overall, Greece is a country of intermediate HAV endemicity. HAV incidence has decreased over the last years and changing epidemiology is related to migration, with well-known risk factors. Higher incidence is observed in the Northern part of the country, among rural populations, and in minorities. Surveillance data have shown that highest HAV incidence has shifted towards older age.
• Results from a study conducted in 2007 among unvaccinated children 1-14 yrs reported that 17.9% had serologic evidence of past natural infection. This finding warrants consideration of implementation of routine vaccination against HAV in Greece.

Epidemiology of HEV in Greece
• Little data are available on HEV epidemiology in Greece except for prevalence estimates available from healthy blood donors (0.23%), healthy workers (2.2%) and hemodialysis patients, for whom higher HEV prevalence was noted (up to 9.7%).
• Based on the few existing data, there appears to be no evidence of HEV endemicity in Greece. However, further research might be considered
on environmental spread and potential animal reservoirs.

Epidemiology of HBV in Greece
• Greece is a country of intermediate HBV endemicity (HBsAg prevalence >2%) with higher incidence in the Northern part of the country, in minorities, and high risk groups. HBV incidence is highest among 15-24 year-olds.
• Over time, HBV incidence has decreased due to the impact of immunization, as well as improvements in socio-economic status and HC system. However, changing epidemiology is also related to migration, with residual reservoirs of carriers and documented intrafamilial spread of HBV.
• Factors influencing current HBV epidemiology include modes of transmission, travelling habits, and immigrants with high HBsAgand HBeAg-positivity rates.

Epidemiology of HCV in Greece
• Greece is a country of low HCV endemicity (<2%) with overall HCV incidence decreasing over time and highest incidence observed in the region of Athens (linked to IDU). The importance of genotype 3 is increasing over time.
• A higher HCV incidence is observed in minorities and high risk groups (blood transfusion, IDU, etc). Some groups with higher HCV rates need better understanding and follow-up actions.
• Risk factors remain through failure of prevention in medical practice and nosocomial risk. As higher HCV prevalence was reported to be associated with some iatrogenic practices (use of glass syringes, non-disposable material, dental practices, surgery, hospitalisation, etc), control and standard precaution measures should be implemented and their importance should be emphasized in (para)medical education. More specifically, the need for further research on the potential implications of high HCV in HCW in some hospitals was identified, since this could represent a risk of further spread as well as an issue of exposure and universal precautions.

Epidemiology of HDV in Greece
No HDV data representative of the general population in Greece are
available. HDV infection mainly occurs in IDU or in specific areas,
while higher rates are also noted in immigrants (study in Albanians:
12.7%). High risk groups include IDU, prisoners, HIV-positive individuals,
sex workers and minorities.

Molecular epidemiology of HBV and HCV
• In accordance with HBV genotype distribution observed in other Mediterranean countries, HBV genotype D is the most frequent in Greece, followed by genotypes A and G.
• The distribution of HCV genotypes in Greece is different from other Mediterranean countries. Several HCV genotypes are detected with a predominance of genotype 1 (particularly in older individuals) and a fast increase in prevalence of genotype 3 since the 1970s (especially in younger individuals).

Migration and viral hepatitis
• Immigrants account for 7-10% of the Greek population, mainly from Albania, other Balkan countries and Post-Soviet countries, leading to changes in HBV and HAV epidemiology in Greece. No routine serological testing is performed in the immigrant population. Health issues in migrant populations need to be documented since they have implications for immigrants as well as for the Greek population.
• High prevalence levels are observed, e.g. up to 22% HBsAg-positivity in Albanian immigrants, 96% anti-HAV-positivity among Albanian pregnant women, and up to 2.3% anti-HCV positivity in immigrants living in Athens.
• Prevalence data among immigrants, only available in a fragmented way, are based on legal individuals only and can therefore be considered as underreported.

HIV and HBV/HCV coinfection
The prevalence of HCV coinfection among HIV patients in Greece is relatively low. Unlike patients infected with HBV but who are HIVnegative, the incidence of HBeAg-positivity is high in coinfected HIV patients in Greece.

National Board of Immunization (NBI)
• NBI is an Advisory Committee to the Greek MOH; members are mainly pediatricians although the board is also responsible for adult immunization recommendations.
• NBI reviews immunization programs, including the introduction of new vaccines, and makes recommendations for targeted patient groups. NBI also ensures the availability and distribution of vaccines and is responsible for reporting vaccine-related safety issues.

Overview of HBV Immunization program in Greece
• 1982: risk group vaccination was introduced
• 1993: start campaign for routine immunization
• 1998: HBV vaccine was included in the National Immunization Program (2, 4, 6-18 month schedule; for infants of HBsAg-positive mothers: birth dose + 1-2, 6-18 month schedule)
• 2006 national coverage survey has shown that 67% of vaccinations are carried out by the private sector. Vaccination coverage in young school children is 95% versus 85% in adolescents; it is evenly distributed among regions with good coverage of immigrants (except Greek Roma children coverage of only 59%). The observed delayed start of HBV vaccination and delayed completion of the primary course increases the risk for chronic carriage.

Overview of HAV Immunization program in Greece
• HAV vaccine is available since 1995 and recommended for risk groups but not included in the National Immunization Program.
• 1/3 of children are vaccinated, mainly by private pediatricians at entrance in day care centre. HAV vaccination coverage is higher in Central and Southern Greece where natural immunity is lower than in the North.
• HAV vaccine is widely used but not necessarily for those who need it most (e.g. immigrant children). As >60% of immunization practices are being performed by the private sector, this may leave unprotected population unvaccinated and contribute to shifting HAV incidence to older age groups.
• Results from a 2006 national coverage survey have shown that 88% of vaccinations are carried out by the private sector. Vaccination coverage
in young school children is 37% versus 22% in adolescents. Large differences in coverage were noted between regions and social groups, with high risk groups (minorities) vaccinated less.
• New cost-effectiveness studies are needed to assist decisionmaking process on HAV vaccination policy, taking into account indirect costs, herd immunity effects, etc.
• Feasibility and timing of HAV vaccine introduction into the National Immunization Program depend on the competition with other vaccines, such as HPV, varicella, rotavirus and pneumococcal vaccines. There is a need to reevaluate routine HAV vaccination or more extended targeted HAV vaccination including other risk groups, in particular immigrant children.

Lessons learnt and challenges
• Prevention and control of viral hepatitis in Greece is the responsibility of a group of remarkable scientists, doctors and public health experts, with a large research output, based on the recognition of viral hepatitis as a well-known public health burden.
• As epidemiological data are often fragmented and not based on representative samples, figures are sometimes surprising. Hence, there is a need for validation in larger representative cohorts: national hepatitis seroprevalence and incidence data as well as reliable surveillance systems are needed. Funding of a national seroprevalence study is a major issue but linking with HIV seroprevalence might increase feasibility.
• Child Health Booklet is a unique source of data on immunization status of children in Greece and is very well kept by the parents.
• The high involvement of the private sector in Greek HC services leads to social inequities. Although the strong involvement of the private sector allows for rapid introduction of new vaccines, it provides no guarantee to cover the whole country, in particular immigrant (7-10%) and lower socio-economic populations. However, the higher HAV, HBV and HCV incidence in immigrants deserves special attention in terms of immunization policy for this population.
• The expertise gained during the 2004 Olympics may be used for the benefit of current surveillance systems and enhanced surveillance could be maintained for routine surveillance by HCDCP.
• Although increasing experience with treatment of HIV-HBV and HIV-HCV co-infected patients exists, there is a further need for long-term follow-up of this population. In these patients, attention should be paid to strengthen primary prevention programs, including harm reduction measures and needle exchange programs. Data relating to preventive measures taken to reduce HIV/HBV/HCV infections in IDUs should be made available.
In addition, HBV vaccination policy as well as HBV and HCV
treatment in HIV-positive patients should be enhanced.

Recommendations for future actions
• Representative cohort studies should be designed and conducted in order to obtain national hepatitis seroprevalence data.
• Future vaccination coverage studies should be conducted, with inclusion of younger age groups, as feasible.
• Campaigns should be set up to stress the importance of timely HBV vaccination and the use of combined vaccines could be promoted, while paying specific attention to related financial issues.
• Early HBV vaccination of infants and catch-up of children and adolescents of immigrant parents with chronic HBV infection should be implemented.
• HAV vaccination programs should be set up for susceptible immigrant children before visiting their endemic home country.
• Greece should make a decision on the introduction of routine HAV vaccination, taking into account elements of the Israelian experience, such as pros and cons of routine vaccination, parameters of the decision-making process involved, context of an area of endemicity in transition, level of contact between high and low socioeconomic groups and the risk for outbreaks, numbers of fulminant HAV cases, in order to set priorities on the basis of cost-benefit analyses and achieve long-term policies.


Further information is available in the corresponding Viral Hepatitis Issue or  meeting web page.