Epidemiology of hepatitis B and D in Greece
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1 Epidemiology of hepatitis B and D in Greece George V. Papatheodoridis Assistant Professor in Medicine & Gastroenterology 2nd Department of Internal Medicine, Athens University Medical School, Hippokration General Hospital, Athens, Greece
2 Epidemiological data for HBV & HDV in Greece No data in samples representative of general population Very few data for the prevalence of HDV Some studies in Specific low-risk groups (blood donors, army recruits, children, pregnant women) Specific high-risk groups (IVDU, prisoners, HIV+, prostitutes, minorities) Specific areas
3 Changing factors affecting the current epidemiology of viral hepatitis Modes of transmission Traveling Globalization Mutants Refugees - Immigrants Changing profile of the population in Greece after 90 (migration) 2001: (7.2%) immigrants 65% from Albania
4 Worldwide prevalence of chronic HBV infection Prevalence of HBsAg >8 % - High 2-7 % - Intemediate < 2 % - Low CDC CDC
5 Hepatitis B: Greece. General Information Estimated HBsAg prevalence in : >3-5% Universal HBV vaccination applied since 1998 Current HBsAg prevalence: Population study: 2.1% (Eur J Epidemiol 2003;18:551). Company employees: 2.6% (Eur J Epidemiol 2001;17:721). Hospitalized patients (Crete): 2.7% (BMC Public Health 2001;1:17)
6 Estimated prevalence of HBsAg and anti-hcv in Greece (general population, blood donors & high risk groups) ,12 2, HBsAg+ (%) anti-hcv+ (%) N= ( ) N= ( )
7 Prevalence of HBV in low-risk groups in Greece
8 Prevalence of HBsAg in blood donors in Athens-Piraeus greater area ( ) HBsAg (+) % 3 2 4,9 4,13 1 0,84 0,34 0 Vissoulis 1972 (n=6708) Blood Bank GSHP ( , n=213167) Kyriakis 2000 ( , n=242625) Kyriakis 2000 ( , n=45504)
9 Epidemiological surveillance in Greek blood donors: (Σ.Κ.ΑΕ.) Prevalence in 41 transfusion centers ( blood units) Positive units Ν % HBsAg Anti-HCV
10 Epidemiology of Hepatitis B: Greece Prevalence of HBsAg Carriage among Army Recruits Region 1972 Athens Metropolitan Area Southern Greece Central Greece Northern Greece Islands (including Crete) National Average Vissoulis et al, 1972; Vakalopoulos et al, in press (N=32,000) 1990 (N=3,200) Change
11 Epidemiology of Hepatitis B: Greece Prevalence of HBsAg Carriage among Army Recruits Region 1972 (N=32,000) Athens Metropolitan Area 3.07% Southern Greece 5.57% Central Greece 5.21% Northern Greece 7.37% Islands (including Crete) 3.20% National Average 5.04% Vissoulis et al, 1972; Vakalopoulos et al, in press 1990 (N=3,200) Change
12 Epidemiology of Hepatitis B: Greece Prevalence of HBsAg Carriage among Army Recruits Region Change (N=32,000) (N=3,200) Athens Metropolitan Area 3.07% 0.86% -72% Southern Greece 5.57% 2.34% -58% Central Greece 5.21% 1.22% -77% Northern Greece 7.37% 2.38% -68% Islands (including Crete) 3.20% 0.70% -78% National Average 5.04% 1.27% -75% Vissoulis et al, 1972; Vakalopoulos et al, in press
13 HBsAg prevalence in Greek army recruits 6 5 4% 4 3.3% HBsAg (+) % 1.2% 1% 1.1% 0.95% * 50-80% decrease of HBsAg prevalence from 70s to 80s Change in risk factors Low vaccination rate in late 90s. 1999: Anti-HBs (+) 32.6% Papaevangelou G, Vaccine 1998 *Stamouli M et al, Eur J Epidemiol 1999
14 HBsAg prevalence in women at reproductive age in Greece % HBsAg (+) women 12 at reproductive 8 age, % % 0.3% 5.1% 1.1% 0.4% 4.2% 0 Albanian Total Greek Albanian Eastern African Asian (n=500) (n=13581) European Malamitsi A et al. Elefsiniotis IS et al. Eur J Epidemiol 1996 J Clin Virol 2005; 32:
15 Origin of HBsAg(+) women at reproductive age in Greece Asia (2.6%) Eastern Europe (7.0%) Africa (1.3%) Greece (17.8%) Albania (71.3%) 4.5% HΒeAg (+) Elefsiniotis IS et al. J Clin Virol 2005; 32:
16 Prevalence of HBV in high-risk groups in Greece
17 HBV infection in anti-hcv (+) Greek IVDU % 82.5% Before 1992 After 1992 (n=103) (n=127) 61.5% % 0% 22% 3.8% 16.5% 10.5% 0 HBsAg(+) anti-hbc(+) Only Anti- HBs(+) Elefsiniotis I et al. Eur J GE Hep 2006; 18: HBV(-)
18 Epidemiological surveillance in Greek IVDU IVDU, n=1094 HBsAg (+): 4,8% anti-hcv (+): 67,9% ΕΚΤΕΠΝ, 2002
19 HBV/HCV infection in prisoners in Greek prisons Prisoners, % % 58.2% 49% % 13% 6,5% 0 IVDU (n=544) Non-IVDU (n=194) HBsAg (+) anti-hbc (+) anti-hcv (+) Malliori M et al. Addiction 1998; 93: Giotakos O et al. Epidemiol Infect 2003; 130:
20 HBV infection in Greek HIV (+) patients 80 HIV+ 60 patients, % % 78% % 12.1% 0 (n=181) (n=737) HΒsAg(+) 61% HΒeAg (+) HBV DNA ( cp/ml) anti-hbc(+) Dimitrakopoulos A et al. J Infect 2000; 40: Elefsiniotis IS et al. J Clin Virol 2005; 32:
21 HBV prevalence in immigrants in Greece 80 71% HBsAg (+) anti-hbc (+) 60 53% % 15% 4% 17% 0 Albanians Albanians Immigrants from in NW Greece in Athens former USSR in Thrace (n=1020) (n=130) (n=463) Dalekos G et al. Roussos A et al. Papoutselis K et al. Eur J GE Hep 1995 World J GE 2003 EASL 2001
22 Prevalence of HBV in specific areas of Greece
23 Age-specific prevalence of HBV infection in selected Greek areas anti-hbc (+) % Archangelos ( ) Alonissos (1986) Plati (1973) Athens ( ) >60 years old Tassopoulos & Papatheodoridis. Hell J Gastroenterol 1993; 6: 67-73
24 HBsAg prevalence in Thrace Indigenous population Moslem minority 11.3% HBsAg (+) % % 5.3% 5.4% 0.6% 2.4% 7.9% Age years Papoutselis K et al. EASL %
25 HBV infection in Greece: Modes of transmission
26 Risk factors associated with acute hepatitis B cases in Greek adults Homosexual activity 12% Unknown 35% 22% Heterosexual activity Health care workers 1% Transfusions 5% 11% Iatrogenic 22% IVDU N= Tassopoulos & Papatheodoridis. Hell J Gastroenterol 1993; 6: 67-73
27 Possible source of infection in Greek adults with chronic HBV infection 7.4% Vertical transmission 16.9% Intrafamilial spread Unknown 64.6% 3.5% Heterosexual contact 4.1% 3.5% Iatrogenic Other HBV cohort KEELPNO, N=3353 G Touloumi, personal communication
28 Intrafamilial spread: the most common mode of transmission in Greeks with chronic HBV infection % 20 Cases, % % 14.1% HBsAg+ anti-hbc % Family members of Blood donors HBV carriers (n=387) (n=6696) Zervou et al. Eur J GE Hepatol 2005; 17: 911-5
29 HBV infection: The burden of disease in Greece
30 HBV: the most common cause of acute viral hepatitis in Greek adults *incl. 0.1% HEV Non-(A-C)* HCV 9% CHB 5.5% 4.5% HAV 14% 67% HBV N= Tassopoulos & Papatheodoridis. Hell J Gastroenterol 1993; 6: 67-73
31 Natural history of chronic HBV infection Immune HBeAg sero- Inactive chronic tolerant conversion phase HBV carrier phase HBeAg(+) CHB state HBeAg(-) CHB 10 HBeAg(+) HBeAg(-)/anti-HBe(+) Serum 8 HBV DNA, log 10 IU/mL ALT ULN Papatheodoridis et al. Lancet Infect Dis 2007; in press
32 Profile of Greek HBsAg(+) patients in primary care % Chronic HBV patients, % % N= % HBeAg(+) HBeAg(-) HBeAg(-) CHB inactive carriers CHB Zacharakis et al. J Med Virol 2005; 77: 173-9
33 Patients with chronic HBV infection at Hippokration hospital, Athens, Greece ( ) % 48% Chronic HBV patients, % N= % HBeAg(+) HBeAg(-) HBeAg(-) CHB/Ci inactive carriers CHB/Ci
34 Patients with chronic HBV infection at Hippokration hospital, Athens, Greece ( ) 60 Chronic HBV patients, % % 41% N= % 0.8% 7% HBeAg(+) HBeAg(-) HBeAg(-) CHB Ci* inactive carriers CHB Ci* *Decompensated Ci
35 Proportion of immigrants among patients with chronic HBV infection in Greek hospitals ( ) % 40 Immigrants, % % 17% 10 0 All HBV+ cases HBV+ adults HBV+ children n=3234 n=3112 n=122 HBV cohort KEELPNO G Touloumi, personal communication
36 Proportion of immigrants among patients with chronic HBV infection at Hippokration hospital, Athens, Greece ( ) % P=0.014 P= Immigrants, % 20 24% 22% 24% 10 0 All HBV+ HBeAg(+) HBeAg(-) HBeAg(-) cases CHB/Ci inactive carriers CHB/Ci n=632 n=39 n=290 n=303
37 HDV Epidemiology in Greece
38 HDV infection HDV + HBV coinfection HDV superinfection HDV + HBV acute infection HDV infection on chronic HBV infection
39 HDV superinfection as a cause of acute hepatitis in chronic HBV patients in Greece HCV 8% 1% 9% HDV+HCV HDV P<0.001 HDV 38% 15% HCV 4% ACHB 42% 82% ACHB Non-IVDU, n=77 IVDU, n=26 HDV +HCV Papatheodoridis et al. Hepatology 1994; 20: 297A
40 HDV as a cause of acute hepatitis in Greek IVDU with acute or chronic hepatitis B P< % HDV (+), % % 0 Acute hepatitis B Chronic hepatitis B n=219 n=31 Tassopoulos et al. Prog Clin Biol Res 1993; 382: 221-7
41 Patients with chronic HBV ± HDV infection at Hippokration hospital, Athens, Greece ( ) % 80 Chronic HBV±HDV patients, % N= % HBV HDV
42 Proportion of cirrhotics among patients with chronic HBV ± HDV infection at Hippokration hospital, Athens, Greece ( ) P<0.001 Patients with decomp. cirrhosis, % % 20 15% 0 HBV HDV excluding carriers n=342 n=23
43 Proportion of immigrants among patients with chronic HBV ± HDV infection at Hippokration hospital, Athens, Greece ( ) P=0.005 Immigrants, % 60 52% % 0 HBV HDV n=632 n=23
44 HBV/HDV Epidemiology in Greece: Summary Decrease of HBsAg prevalence over the past decades Improvement of social-economic status Improvement in health care system Better awareness of high-risk groups Vaccination Still areas of high HBsAg prevalence Surveillance Increasing age of chronic HBV patients: increasing probability of clinical events (decompens., HCC) HDV: mainly in IVDU or specific areas More severe disease Immigrants after 1990: 1/10-1/12 of Greek population High HBsAg prevalence Higher rates of HBeAg(+) Younger age, HBV genotypes Higher rates of HDV infection
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