- Email: [email protected]
Hepatitis C virus infection in Eastern Europe
Journal of Hepatology 1999: 31: (Suppl. 1): 84-87 Printed in Denmark . AN rights reserved Mtmksgaard . Copenhagen
Copyright 0 European Association for the Study of the Liver 1999
Journal of Hepatology ISSN 0169-5185 ISBN 87-16-16386-9
Hepatitis C virus infkction in Eastern Europe Nikolai V Naoumov Institute of Hepatology,
University College London, London, England
This analysis aims to smmnarise the available information on the incidence, prevalence and characteristics of hepatitis C virus (HCV) infection in countries in Eastern Europe. ikfetk&: A questionnaire was prepared on the epidemiology and diagnosis of HCV infection and sent to national experts in the field. Further information was obtained from publications in international and national scientific journals. The incidence of acute hepatitis C in different countries for 1997 varied between 2.3 and 9.0 per 100 000 population with a trend towards increasing numbers of cases in several countries over the last few years, The prevalence of anti-HCV in blood donors ranged between 0.7% and 4.9%. The most frequent routes of transmission of HCV appear to be diagnostic and therapeutic procedures in the health care setting and/
I
with hepatitis C virus (HCV) is a major cause of liver disease, cirrhosis and hepatocellular carcinoma worldwide. Eastern Europe comprises 19 countries with approximately 345 million people. At present, there is limited information on the magnitude and the characteristics of HCV infection in this part of the continent. The aim of this review was to present data on the incidence and prevalence of HCV infection in countries in Eastern Europe and to identify specific features of the infection in this region. For this purpose we prepared a questionnaire on the main aspects of the epidemiology and diagnosis of HCV infection, which was sent to experts dealing with patients with HCV infection in the countries in Eastern Europe. In addition, papers published in international and major national journals provided further information. NFECTION
Correspondence: Dr. Nikolai Naoumov, Institute of Hepatology, University College London, 69-75, Chenies Mews, London WClE 6HX, England. Tel: +44-171-388 2013. Fax: +44-171-380 e-mail: [email protected]
84
0405.
or intravenous drug use. Cumulative data on HCV genotype distribution based on 1774 patients demonstrate a large predominance of genotype lb, which is found in between 51% and 92% of patients with HCV infection. There is a high prevalence of HCV infection in Eastern Europe. Further studies with larger groups of patients and especially including molecular diagnostic assays are needed to better deiine the characteristics of HCV infection, its natural course and the impact of host and viral factors on the HCWnduced liver diseases. These will have a major role for adequate selection and monitoring of the patients’ treatment.
Key wovds: Eastern Europe; Epidemiology; Hepatitis C incidence; Prevalence.
Incidence and prevalence of HCV infection The incidence for 1997 of registered cases of acute hepatitis C in different countries in Eastern Europe varies between 2.2 and 9.0 per 100 000 population. The age distribution of patients with acute hepatitis C in Bulgaria, the Czech Republic and Russia shows a common trend, as the highest incidence was found amongst young people aged 15-19 (Bulgaria 2.41100 000 and Czech Republic 8.61100 000) or aged 2629 (Russia between 16 and 40/100 000). Morbidity from acute hepatitis C in Lithuania (Vilnius) for 1991-92 was 9.1/ 100 000 and the distribution according to age groups shows the highest rate for ages 30-39 and 4&49 (1). A comparison of the figures for the last few years shows an increasing frequency of acute hepatitis C in several countries - Czech Republic, Estonia, Poland and Russia. For example, the average incidence of acute hepatitis C in the Russian Federation was 3.19/100 000 population in 1994; 6.81/100 000 in 1995; 8.4/100 000 in 1996 and 9.0/100 000 in 1997 (V Ivashkin - personal communication). Although the incidence of acute hepatitis C varies considerably in different regions in
HCV in Eastern Europe
the Russian Federation (from 3.7 in Central Chernoziomni region, to 8.4 in Volga and up to 18.3 in the Kaliningrad province), the trend of an increasing number of cases with acute hepatitis C is present in all regions. The prevalence of HCV infection has been studied in blood donors, in high risk groups and in patients with liver diseases using 2nd or 3rd generation enzyme immunoassays for the detection of anti-HCV (Abbott, UBI and Ortho) and 2nd and 3rd generation immunoblot assays (Ortho Diagnostics). Data on the prevalence of anti-HCV amongst blood donors from 10 countries show a wide range of anti-HCV positivity, from 0.68% in the Czech Republic to 4.9% in the Iasi district in Romania (2) (Table 1). A similarly high prevalence of HCV infection amongst blood donors in Romania was found in another study, which included cases from Bucharest (4.3’). Apart from the prevalence of HCV infection in blood donors, studies from several countries have tested the prevalence of HCV infection in certain high risk groups (Table 1). A high prevalence of HCV infection has been demonstrated in patients with haemophilia: Bulgaria 78% (4) and Poland 59% (5), and in patients on haemodialysis: Bulgaria, 97 of 231 patients tested - 42% (6); Poland, 81 of 142 patients - 57% (5); and Lithuania, 28 of 58 - 48% (1). In several studies the prevalence of HCV infection has been investigated in the medical staff working in departments with a greater risk of acquiring HCV infection. When testing the personnel in haemodialysis centres in Bulgaria, two of 114 (1.8O/,) were anti-HCV positive (6); in the Czech Republic - two of 150 (1.3%); and in Lithuania - 11 of 140 medical personnel (7.9%) (1). One study investigated the prevalence of anti-HCV in 409 health care workers at the Central Hospital for infectious diseases in Budapest, Hungary (7). Ten of 409 tested (2.4%) were found to be anti-HCV positive (all confirmed by RIBA 3.0 Ortho), which included eight nurses, one of the sanitary personnel and one laboratory technician. None of the doctors tested positive for anti-HCV (7).
Routes of transmission The information available indicates a major role of nosocomial transmission of HCV in countries in Eastern Europe (Table 2). Diagnostic or treatment procedures in hospitals were indicated as the source of infection in approximately 59-65% of cases in Poland (5, 8), 59% in Latvia (L. Viksna - personal communication) and 46% in Lithuania (9). A study including 711 patients from Bucharest who were seropositive for anti-HCV, identified the relative importance of different routes as follows: parenteral procedures in hospi-
TABLE 1 Prevalence of HCV infection in specific groups in several countries in Eastern Europe (%) Country
Blood donors
Patients with Patients on Medical haemophilia haemodialysis personnel
Bulgaria Czech Republic Estonia Hungary Latvia Lithuania Poland Romania Russia Ukraine
1.4 0.68 1.0 0.75 1.2 2.2 1.4 4.9 1.6 2.3
18 59
42 42
1.2 1.0 - 2.0
50
nk
3.1
nk 59 92 nk
48 57 nk 13
2.0 - 1.9 nk nk 0 - 10.0
The data for this table have been obtained from references l-6 and 14-17 as well as from the questionnaire, which was completed by a representative from the countries shown. nk - not known.
TABLE 2 Relative importance of different routes of transmission of HCV (%) Country
Blood IVDU transfusion
Nosocomial (surgery or parenteral procedures)
Czech Republic Latvia Lithuania Hungary Poland Romania
nk
92.0
nk
3.6 16.7 25 nk 14.5
10.0 nk 0.5 nk nk
4
3&75
58.7 46.7 40.0 59-65 71.0 (21.2 surgery and 49.8 procedures) 1624
Russia
Sexual Unknown and/or Other 2.0
6.0
13.0 3.3 0.5 nk nk
14.7 33.3 34.0 nk 14.5
3-16
nk
The data for this table have been obtained from refs. 1, 5, 8-10 and 18, as well as from the questionnaire, which was completed by a representative from these countries. nk - not known.
tals 49.8%, surgery 21.2% and blood transfusion 14.5% (10). When testing 100 unselected parenteral drug users in Warsaw, 76% were found to be seroposiitve for antiHCV and there was no significant association with age or duration of drug use (11). Data from the Czech Republic, based on the National Epidemiological Register of 190 patients with acute hepatitis C, indicate the use of intravenous drugs as a route of infection in 92% of the cases (J. Spicak - personal communication). Thus, the available data indicate that blood transfusion is not the main route of transmission of HCV The differences in the relative importance of nosocomial or intravenous drug use as main routes of transmission of HCV, may be due to the fact that the studies targeted different patient populations and/or because 8.5
N. V. Naoumov
of a relatively small sample size; further needed to clarify this.
studies are
are used mainly for research purposes rather than for routine diagnosis and not for all, cases found to be anti-HCV seropositive.
Distribution of HCV genotypes From the published literature and the response to the questionnaire, information has been collected on the distribution of HCV genotypes in 1774 patients with HCV infection from 12 countries in Eastern Europe (Table 3). This reveals an important feature of HCV infection in this part of Europe because in all countries most cases are infected with HCV genotype lb - between 51% and 92% of the patients tested. Two independent studies from Croatia (involving 203 patients) and from Slovenia (also with 203 patients) showed a marked difference in the distribution of HCV genotypes according to the route of transmission (12, 13). In both studies, HCV genotype lb was most frequently found in patients who acquired infection via blood transfusion, while HCV genotype 3 was predominant among intravenous drug users.
Diagnosis of HCV infection The screening of donated blood for anti-HCV has been introduced at different times in the 1990s: 1992 - Czech Republic and Hungary; 1993 - Latvia and Lithuania; 1994 - Bulgaria, Estonia and Russia. For the diagnosis of HCV infection, 2nd and mostly 3rd generation immunoassays are being used (Abbott, UBI and Ortho), as well as immunoblot assays (Ortho Diagnostics). These are performed at blood banks and in laboratories at departments or hospitals for infectious diseases. The use of molecular assays (for the detection and characterisation of HCV RNA) is usually centralised in a small number of laboratories (between one and five laboratories in individual countries, four in Moscow). These assays
Conclusions There is a high prevalence of HCV infection in Eastern Europe, which is characterised by a predominance of HCV genotype lb. The incidence of cases with acute hepatitis C did not decrease significantly after introducing blood screening. The most frequent routes of transmission of HCV appear to be diagnostic and therapeutic procedures in the health care setting and/ or intravenous drug use. Studies so far have mainly investigated the prevalence of infection in different groups, whereas the natural course of HCV infection and the impact of specific factors on the disease have not been analysed. Further studies are needed to investigate the prevalence and incidence of HCV infection in countries and regions in Eastern Europe for which there is no information. In addition, studies in larger groups of the population, especially in high risk groups, would be important to more accurately evaluate the magnitude of HCV infection. The most important need seems to be to plan and carry out studies on the natural course of acute and chronic HCV infection in Eastern Europe and on the impact of specific factors on the course of liver disease. For this purpose, as well as for the selection of patients for treatment, there is a need for a wider application of molecular assays in the diagnosis and management of cases with HCV infection. Based on data from preliminary studies on the main routes of HCV transmission, measures to reduce nosocomial transmission and intravenous drug use are likely to have a major impact on decreasing the incidence of cases with HCV infection.
TABLE 3 Distribution of HCV genotypes in Eastern Europe (%) Country No. cases Genotype la lb 2 3 Mixed Other or unknown
BLR
BG
CZECH
CR0
EST
HUN
LAT
LTH
MOL
POL
RUS
SLO
110
244
17
101
95
137
413
71
50.9 20.0 13.6 14.5 1.0
2.0 90.0 3.0 2.0 3.0
64.7 5.9 29.4 -
2.0 53.5 6.9 4.9 32.7 -
4.2 91.6 3.2 -
1.5 83.9 0.7 7.3 2.9 6.8
10.2 66.3 5.1 12.4 0.8 5.2
25.0 54.0 5.0 16.0 -
41
121
221*
203
2.4 75.6 2.4 19.6
2.5 76.8 1.7 12.4 6.6
;
11.0 61.0 1.0 26.0 1
-
83.7 5.9 3.2 3.6 3.6
BG - Bulgaria; CZECH - Czech Republic; EST - Estonia; HUN - Hungary; LAT - Latvia; LTH - Lithuania; ROM - Romania; RUS - Russia (Ulyanovsk); UKR - Ukraine, BLR - Belarus; CR0 - Croatia; MOL - Moldova; SLO - Slovenia. * Serotyping by Murex HCV serotyping assay. nk - not known.
86
HCV in Eastern Europe
Acknowledgement This review was possible only with the help and the information provided by experts from several countries: Professor Arvydas Ambrozaitis (Vilnius, Lithuania); Professor Anna Boron-Kaczmarska (Szczecin, Poland); Assoc. Professor Pencho Draganov (Sofia, Bulgaria); Professor Vladimir Ivashkin (Moscow, Russia); Professor Alajos Par (Pets, Hungary); Assoc. Professor Riina Salupere (Tartu, Estonia); Assoc. Professor Julius Spicak (Prague, Czech Republic) and Professor Ludmila Viksna (Riga, Latvia). The author is grateful to the above colleagues for their valuable contribution to this work.
References 1. Ambrozaitis A, Zagminas K, Balciunaite G, Wide11A. Hepatitis C in Lithuania: incidence, prevalence, risk factors and viral genotypes. Clin Diagn Virol 1995: 4: 273-284. 2. Ivan A, Azoicai D, Grigorescu R, Pisica G, Groll M, Trifan M et al. Seroepidemiological considerations of the incidence of viral hepatitis C in some population groups. Rev Med Chir Sot Med Nat Iasi 1995: 99: 1299138 (in Romanian). 3. Antipa C, Popescu A, Teleguta M, Ruta S, Cernescu C, Tardei G et al. Seroprevalence of hepatitis C virus among the multiply transfused. Rom J Virol 1993: 44: 9-15 (in French). 4. Naoumov NV, Lissichkov T, Rumi MG. Hepatitis C virus infection in hemophiliacs in Bulgaria. Ann Intern Med 1991: 114: 171-172. 5. Polz MA, Rajtar B, Daniluk J, Kowalczyk J, Ksiazek A, Pokora J. Infection with HCV in patients hospitalized for various causes. I. Prevalence of anti-HCV antibodies in selected groups of patients. Przegl Epidemiol 1995: 49: 313-316 (in Polish). 6. Draganov P, Teoharov E Dimitrova T, Ivanova R, Kirjakov Z, Mushikov V et al. Prevalence of HCV infection among patients and medical staff in haemodialysis centres. Infectology 1994: 31: 32-35 (in Bulgarian). 7. Mihaly I, Lukacs A, Telegdy L, Ibrabyi E. Prevalence of hepatitis C antibody in hospital personnel. Orvosi Hetilap 1996: 137: 2791-2794 (in Hungarian). 8. Wartmek W, Librant-Suska M, Krukowiecki J, Zejc-Bajsarowicz M, Janas-Skulina U, Garlikcki A. Epidemiologic and clinical characteristics of patients with hepatitis type C. Folia Med Cracov 1996: 37: 71-79 (in Polish). 9. Speiciene D, Ambrozaitis A, Irnius A, Semuchiniene T, Anuseviciene R. Hepatitis C virus infection in chronic liver disease of vari-
ous etiology in Lithuania. Prevalence and risk factors. Acta Med Lituanica 1995: 4: l&17. 10. Buligescu L, Mihaila M, Topala D. Signiiicance of epidemiological ways of transmission of HCV infection. J Hepatol 1997: 26, Suppl. 1: 231. 11. Laskus T, Radkowski M, Lupa E, Slusarczyk J, Cianciara J, Halama G et al. Prevalence of markers of hepatotropic viruses among drug addicts in Warsaw, Poland. J Hepatol 1992: 15: 114 117. 12. Vince A, Palmovic D, Kutela N, Sonicky Z, Jeren T, Radovani M. HCV genotypes in patients with chronic hepatitis C in Croatia. Infection 1998: 26: 173-177. 13. Seme K, Poljak M, Lesnicar G, Brinovec V, Stepec S, Koren S. Distribution of hepatitis C virus genotypes in Slovenia. Stand J Infect Dis 1997: 29: 29-31. 14. Tretskaia TA, Shakhgil’dian IV, Iashina TL, Kravchenko VK, Liubchak VA, Mikhno LA et al. The incidence of detecting hepatitis C viral antibodies in different age groups of the population in north eastern Ukraine. Vopr Virus01 1993: 38: 137-138 (in Russian). 15. Ariamkina OL, Grigor’ev IB, Fadeeva GE, Burganova RA, Maiorova GS, Khalilova RR et al. The diagnosis of hepatitis C viral infection in blood donors and patients. Zh Mikrobiol Epidemiol Immunobiol 1998: 1: 74-77 (in Russian). 16. Tamme J, Rahu M, Kallassalu H, Sultsmann M-K, Lemming L, Veske M. Prevalence of hepatitis C antibodies among blood doors in Estonia (1995-96). Eesti Arst 1997: 6: 49&493 (in Estonian). 17. Rozentale B, Viksna L. Clinical and epidemiological characteristics of acute hepatitis C. Symposium on blood borne virus infections, Riga, Latvia, 2627 May 1998. 18. Juszczyk J, Gladysz A. Viral hepatitis in Poland. Hepatol Polska 1997: 4: 65-70. 19. Lvov DK, Samokhvalov EI, Tsuda F, Selivanov NA, Okamoto H, Stakhanova VM et al. Prevalence of hepatitis C virus and distribution of its genotypes in Northern Eurasia. Arch Virol 1996: 141: 1613-1622. 20. Viazov S, Kuzin S, Paladi N, Tchernovetsky M, Isaeva E, Mahzul L et al. Hepatitis C virus genotypes in different regions of the former Soviet Union (Russia, Belarus, Moldova and Uzbekistan). J Med Virol 1997: 53: 36-40. 21. Jarvis LM, Ludlam CA, Ellender JA, Nemes L, Field SP, Song E et al. Investigation of the relative infectivity and pathogenicity of different hepatitis C virus genotypes in hemophiliacs. Blood 1996: 87: 3007-3011. 22. Par A, Paal M, Gogl A, Gervain J, Szekeres-Barth0 J, Sipos J et al. Chronic hepatitis C: Clinical and immunological features and the effect of interferon treatment. Int J Immunotherapy 1995: 11: 115-127. 23. Ambrozaitis A, Balciunaite G, Wide11A. Hepatitis C virus genotype distribution in Lithuanian first time blood donors. Acta Med Lituanica 1994: 4: 21-24.
87
Copyright 0 European Association for the Study of the Liver 1999
Journal of Hepatology ISSN 0169-5185 ISBN 87-16-16386-9
Hepatitis C virus infkction in Eastern Europe Nikolai V Naoumov Institute of Hepatology,
University College London, London, England
This analysis aims to smmnarise the available information on the incidence, prevalence and characteristics of hepatitis C virus (HCV) infection in countries in Eastern Europe. ikfetk&: A questionnaire was prepared on the epidemiology and diagnosis of HCV infection and sent to national experts in the field. Further information was obtained from publications in international and national scientific journals. The incidence of acute hepatitis C in different countries for 1997 varied between 2.3 and 9.0 per 100 000 population with a trend towards increasing numbers of cases in several countries over the last few years, The prevalence of anti-HCV in blood donors ranged between 0.7% and 4.9%. The most frequent routes of transmission of HCV appear to be diagnostic and therapeutic procedures in the health care setting and/
I
with hepatitis C virus (HCV) is a major cause of liver disease, cirrhosis and hepatocellular carcinoma worldwide. Eastern Europe comprises 19 countries with approximately 345 million people. At present, there is limited information on the magnitude and the characteristics of HCV infection in this part of the continent. The aim of this review was to present data on the incidence and prevalence of HCV infection in countries in Eastern Europe and to identify specific features of the infection in this region. For this purpose we prepared a questionnaire on the main aspects of the epidemiology and diagnosis of HCV infection, which was sent to experts dealing with patients with HCV infection in the countries in Eastern Europe. In addition, papers published in international and major national journals provided further information. NFECTION
Correspondence: Dr. Nikolai Naoumov, Institute of Hepatology, University College London, 69-75, Chenies Mews, London WClE 6HX, England. Tel: +44-171-388 2013. Fax: +44-171-380 e-mail: [email protected]
84
0405.
or intravenous drug use. Cumulative data on HCV genotype distribution based on 1774 patients demonstrate a large predominance of genotype lb, which is found in between 51% and 92% of patients with HCV infection. There is a high prevalence of HCV infection in Eastern Europe. Further studies with larger groups of patients and especially including molecular diagnostic assays are needed to better deiine the characteristics of HCV infection, its natural course and the impact of host and viral factors on the HCWnduced liver diseases. These will have a major role for adequate selection and monitoring of the patients’ treatment.
Key wovds: Eastern Europe; Epidemiology; Hepatitis C incidence; Prevalence.
Incidence and prevalence of HCV infection The incidence for 1997 of registered cases of acute hepatitis C in different countries in Eastern Europe varies between 2.2 and 9.0 per 100 000 population. The age distribution of patients with acute hepatitis C in Bulgaria, the Czech Republic and Russia shows a common trend, as the highest incidence was found amongst young people aged 15-19 (Bulgaria 2.41100 000 and Czech Republic 8.61100 000) or aged 2629 (Russia between 16 and 40/100 000). Morbidity from acute hepatitis C in Lithuania (Vilnius) for 1991-92 was 9.1/ 100 000 and the distribution according to age groups shows the highest rate for ages 30-39 and 4&49 (1). A comparison of the figures for the last few years shows an increasing frequency of acute hepatitis C in several countries - Czech Republic, Estonia, Poland and Russia. For example, the average incidence of acute hepatitis C in the Russian Federation was 3.19/100 000 population in 1994; 6.81/100 000 in 1995; 8.4/100 000 in 1996 and 9.0/100 000 in 1997 (V Ivashkin - personal communication). Although the incidence of acute hepatitis C varies considerably in different regions in
HCV in Eastern Europe
the Russian Federation (from 3.7 in Central Chernoziomni region, to 8.4 in Volga and up to 18.3 in the Kaliningrad province), the trend of an increasing number of cases with acute hepatitis C is present in all regions. The prevalence of HCV infection has been studied in blood donors, in high risk groups and in patients with liver diseases using 2nd or 3rd generation enzyme immunoassays for the detection of anti-HCV (Abbott, UBI and Ortho) and 2nd and 3rd generation immunoblot assays (Ortho Diagnostics). Data on the prevalence of anti-HCV amongst blood donors from 10 countries show a wide range of anti-HCV positivity, from 0.68% in the Czech Republic to 4.9% in the Iasi district in Romania (2) (Table 1). A similarly high prevalence of HCV infection amongst blood donors in Romania was found in another study, which included cases from Bucharest (4.3’). Apart from the prevalence of HCV infection in blood donors, studies from several countries have tested the prevalence of HCV infection in certain high risk groups (Table 1). A high prevalence of HCV infection has been demonstrated in patients with haemophilia: Bulgaria 78% (4) and Poland 59% (5), and in patients on haemodialysis: Bulgaria, 97 of 231 patients tested - 42% (6); Poland, 81 of 142 patients - 57% (5); and Lithuania, 28 of 58 - 48% (1). In several studies the prevalence of HCV infection has been investigated in the medical staff working in departments with a greater risk of acquiring HCV infection. When testing the personnel in haemodialysis centres in Bulgaria, two of 114 (1.8O/,) were anti-HCV positive (6); in the Czech Republic - two of 150 (1.3%); and in Lithuania - 11 of 140 medical personnel (7.9%) (1). One study investigated the prevalence of anti-HCV in 409 health care workers at the Central Hospital for infectious diseases in Budapest, Hungary (7). Ten of 409 tested (2.4%) were found to be anti-HCV positive (all confirmed by RIBA 3.0 Ortho), which included eight nurses, one of the sanitary personnel and one laboratory technician. None of the doctors tested positive for anti-HCV (7).
Routes of transmission The information available indicates a major role of nosocomial transmission of HCV in countries in Eastern Europe (Table 2). Diagnostic or treatment procedures in hospitals were indicated as the source of infection in approximately 59-65% of cases in Poland (5, 8), 59% in Latvia (L. Viksna - personal communication) and 46% in Lithuania (9). A study including 711 patients from Bucharest who were seropositive for anti-HCV, identified the relative importance of different routes as follows: parenteral procedures in hospi-
TABLE 1 Prevalence of HCV infection in specific groups in several countries in Eastern Europe (%) Country
Blood donors
Patients with Patients on Medical haemophilia haemodialysis personnel
Bulgaria Czech Republic Estonia Hungary Latvia Lithuania Poland Romania Russia Ukraine
1.4 0.68 1.0 0.75 1.2 2.2 1.4 4.9 1.6 2.3
18 59
42 42
1.2 1.0 - 2.0
50
nk
3.1
nk 59 92 nk
48 57 nk 13
2.0 - 1.9 nk nk 0 - 10.0
The data for this table have been obtained from references l-6 and 14-17 as well as from the questionnaire, which was completed by a representative from the countries shown. nk - not known.
TABLE 2 Relative importance of different routes of transmission of HCV (%) Country
Blood IVDU transfusion
Nosocomial (surgery or parenteral procedures)
Czech Republic Latvia Lithuania Hungary Poland Romania
nk
92.0
nk
3.6 16.7 25 nk 14.5
10.0 nk 0.5 nk nk
4
3&75
58.7 46.7 40.0 59-65 71.0 (21.2 surgery and 49.8 procedures) 1624
Russia
Sexual Unknown and/or Other 2.0
6.0
13.0 3.3 0.5 nk nk
14.7 33.3 34.0 nk 14.5
3-16
nk
The data for this table have been obtained from refs. 1, 5, 8-10 and 18, as well as from the questionnaire, which was completed by a representative from these countries. nk - not known.
tals 49.8%, surgery 21.2% and blood transfusion 14.5% (10). When testing 100 unselected parenteral drug users in Warsaw, 76% were found to be seroposiitve for antiHCV and there was no significant association with age or duration of drug use (11). Data from the Czech Republic, based on the National Epidemiological Register of 190 patients with acute hepatitis C, indicate the use of intravenous drugs as a route of infection in 92% of the cases (J. Spicak - personal communication). Thus, the available data indicate that blood transfusion is not the main route of transmission of HCV The differences in the relative importance of nosocomial or intravenous drug use as main routes of transmission of HCV, may be due to the fact that the studies targeted different patient populations and/or because 8.5
N. V. Naoumov
of a relatively small sample size; further needed to clarify this.
studies are
are used mainly for research purposes rather than for routine diagnosis and not for all, cases found to be anti-HCV seropositive.
Distribution of HCV genotypes From the published literature and the response to the questionnaire, information has been collected on the distribution of HCV genotypes in 1774 patients with HCV infection from 12 countries in Eastern Europe (Table 3). This reveals an important feature of HCV infection in this part of Europe because in all countries most cases are infected with HCV genotype lb - between 51% and 92% of the patients tested. Two independent studies from Croatia (involving 203 patients) and from Slovenia (also with 203 patients) showed a marked difference in the distribution of HCV genotypes according to the route of transmission (12, 13). In both studies, HCV genotype lb was most frequently found in patients who acquired infection via blood transfusion, while HCV genotype 3 was predominant among intravenous drug users.
Diagnosis of HCV infection The screening of donated blood for anti-HCV has been introduced at different times in the 1990s: 1992 - Czech Republic and Hungary; 1993 - Latvia and Lithuania; 1994 - Bulgaria, Estonia and Russia. For the diagnosis of HCV infection, 2nd and mostly 3rd generation immunoassays are being used (Abbott, UBI and Ortho), as well as immunoblot assays (Ortho Diagnostics). These are performed at blood banks and in laboratories at departments or hospitals for infectious diseases. The use of molecular assays (for the detection and characterisation of HCV RNA) is usually centralised in a small number of laboratories (between one and five laboratories in individual countries, four in Moscow). These assays
Conclusions There is a high prevalence of HCV infection in Eastern Europe, which is characterised by a predominance of HCV genotype lb. The incidence of cases with acute hepatitis C did not decrease significantly after introducing blood screening. The most frequent routes of transmission of HCV appear to be diagnostic and therapeutic procedures in the health care setting and/ or intravenous drug use. Studies so far have mainly investigated the prevalence of infection in different groups, whereas the natural course of HCV infection and the impact of specific factors on the disease have not been analysed. Further studies are needed to investigate the prevalence and incidence of HCV infection in countries and regions in Eastern Europe for which there is no information. In addition, studies in larger groups of the population, especially in high risk groups, would be important to more accurately evaluate the magnitude of HCV infection. The most important need seems to be to plan and carry out studies on the natural course of acute and chronic HCV infection in Eastern Europe and on the impact of specific factors on the course of liver disease. For this purpose, as well as for the selection of patients for treatment, there is a need for a wider application of molecular assays in the diagnosis and management of cases with HCV infection. Based on data from preliminary studies on the main routes of HCV transmission, measures to reduce nosocomial transmission and intravenous drug use are likely to have a major impact on decreasing the incidence of cases with HCV infection.
TABLE 3 Distribution of HCV genotypes in Eastern Europe (%) Country No. cases Genotype la lb 2 3 Mixed Other or unknown
BLR
BG
CZECH
CR0
EST
HUN
LAT
LTH
MOL
POL
RUS
SLO
110
244
17
101
95
137
413
71
50.9 20.0 13.6 14.5 1.0
2.0 90.0 3.0 2.0 3.0
64.7 5.9 29.4 -
2.0 53.5 6.9 4.9 32.7 -
4.2 91.6 3.2 -
1.5 83.9 0.7 7.3 2.9 6.8
10.2 66.3 5.1 12.4 0.8 5.2
25.0 54.0 5.0 16.0 -
41
121
221*
203
2.4 75.6 2.4 19.6
2.5 76.8 1.7 12.4 6.6
;
11.0 61.0 1.0 26.0 1
-
83.7 5.9 3.2 3.6 3.6
BG - Bulgaria; CZECH - Czech Republic; EST - Estonia; HUN - Hungary; LAT - Latvia; LTH - Lithuania; ROM - Romania; RUS - Russia (Ulyanovsk); UKR - Ukraine, BLR - Belarus; CR0 - Croatia; MOL - Moldova; SLO - Slovenia. * Serotyping by Murex HCV serotyping assay. nk - not known.
86
HCV in Eastern Europe
Acknowledgement This review was possible only with the help and the information provided by experts from several countries: Professor Arvydas Ambrozaitis (Vilnius, Lithuania); Professor Anna Boron-Kaczmarska (Szczecin, Poland); Assoc. Professor Pencho Draganov (Sofia, Bulgaria); Professor Vladimir Ivashkin (Moscow, Russia); Professor Alajos Par (Pets, Hungary); Assoc. Professor Riina Salupere (Tartu, Estonia); Assoc. Professor Julius Spicak (Prague, Czech Republic) and Professor Ludmila Viksna (Riga, Latvia). The author is grateful to the above colleagues for their valuable contribution to this work.
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