SPREMLJANJE OKUŽBE Z VIRUSOM HEPATITISA C MED SLOVENSKIMI NOSEČNICAMI

Kopilović, Boris (author), Klavs, Irena (mentor), Poljak, Mario (co-mentor)

Namen dela: Na do sedaj največjem vzorcu nosečnic v svetu smo želeli oceniti spreminjanje prevalence okužbe z virusom hepatitisa C (HCV) v 15-letnem obdobju z metodologijo ponavljajočih se presečnih raziskav z nevezanim anonimnim testiranjem ostankov serumov, ki so bili odvzeti nosečnicam. Rezultate smo primerjali s prevalenco med krvodajalkami enake starosti, da bi sklepali o prevalenci okužbe s HCV in njenem spreminjanju med ženskami v rodni starosti. Cilji in hipotezi: Želeli smo oceniti prevalenco okužbe s HCV med slovenskimi nosečnicami in opisati njeno spreminjanje s ponavljajočimi se presečnimi raziskavami v obdobju 1999-2013 in rezultate primerjati s prevalenco med slovenskimi krvodajalkami. Preverili smo hipotezi: (a) prevalenca okužbe s HCV med slovenskimi nosečnicami se je postopoma zniževala od 1999 do 2013; (b) prevalenca okužbe s HCV med slovenskimi nosečnicami starimi 20-29 let v letih 1999, 2003, 2009 in 2013 je bila višja od prevalence med slovenskimi krvodajalkami starimi 20-29 let. Utemeljitev: Podatkov o prevalenci okužb s HCV v slovenski populaciji in njenem spreminjanju nismo imeli. V številnih državah so prevalenco okuženih s HCV ocenjevali v priložnostnih vzorcih nosečnic. Po dosegljivih podatkih, nihče ni naredil raziskave, ki bi ugotavljala, kako se je med nosečnicami prevalenca spreminjala. Metode: Uvedli smo metodo ponavljajočih se presečnih raziskav za spremljanje spreminjanja prevalence okužbe s HCV z nevezanim anonimnim testiranjem ostankov serumov odvzetih za namene presejanja nosečnic na sifilis. Uporabili smo serume banke serumov Nacionalnega inštituta za javno zdravje, ki so bili zbrani v letih 1999, 2003, 2009 in 2013 v mreži laboratorijev, ki izvajajo testiranje na sifilis, za namen epidemiološkega spremljanja spreminjanja prevalence okužbe s HIV z nevezanim anonimnim testiranjem. Vzorce smo testirali na anti-HCV. Vse anti-HCV reaktivne vzorce smo testirali na HCV RNK in določili genotipe. Z deskriptivnimi statističnimi metodami smo opisali prevalenco okužbe s HCV pri nosečnicah različnih starosti v teh letih in rezultate za 20-29 let stare primerjali z ocenami prevalence za krvodajalke enake starosti. Rezultati: Med skupno 31.849 testiranih vzorcev je bilo 41 anti-HCV pozitivnih (0,13 %; 95 % interval zaupanja (IZ): 0,09 % - 0,17 %) in 29 HCV RNK pozitivnih (0,09 %; 95 % IZ: 0,06 % - 0,13 %). Ocene letne prevalence okužb s HCV (prevalence HCV RNK) so se gibale med 0,06 % (95 % IZ: 0,02 % - 0,14 %) in 0,14 % (95 % IZ: 0,07 % - 0,25 %) (p>0,05). Tako nisem potrdil hipoteze, da se je prevalenca okužbe s HCV med slovenskimi nosečnicami postopoma zniževala od 1999 do 2013. Tudi med starostnimi skupinami (manj kot 20 let, 20-29 let in 30 let ali več) v opazovanih letih ni bilo razlik (p>0,05). V letih 2003, 2009 in 2013 je bila prevalenca okužbe s HCV med slovenskimi krvodajalkami v starostni skupini 20-29 let 0 % (enostranski, 97,5 % IZ: 0,00 % - 0,06 %). V istih letih je bila prevalenca okužbe s HCV med slovenskimi nosečnicami starimi 20-29 let 0,11 % (95 % IZ: 0,06 % - 0,18 %). Potrdil sem hipotezo, da je bila prevalenca okužbe s HCV med slovenskimi nosečnicami starimi 20-29 let v letih 2003, 2009 in 2013 višja od prevalence okužbe s HCV med slovenskimi krvodajalkami starimi 20-29 let. Razpravljanje in zaključek: Na največjem vzorcu nosečnic v svetu in za najdaljše obdobje spremljanja (15 let) smo v Sloveniji prvič pridobili podatke o prevalenci okužbe s HCV med nosečnicami z uvedbo nove in cenovno ugodne metode epidemiološkega spremljanja s ponavljajočimi se presečnimi raziskavami z nevezanim anonimnim testiranjem na okužbo s HCV v lahko dosegljivih priložnostnih vzorcih nosečnic. Ocenjena prevalenca je bila nižja od vseh doslej objavljenih ocen za prevalenco okužbe s HCV med nosečnicami v evropskih državah in se v tem obdobju ni pomembno spremenila. V Sloveniji ne moremo priporočati presejanja nosečnic na HCV. Nosečnice predstavljajo bolj primerno skupino žensk v rodni starosti za sklepanje o prevalenci okužbe s HCV in njenem spreminjanju med ženskami v splošnem prebivalstvu kot krvodajalke iste starosti. Na osnovi teh rezultatov lahko sklepamo, da je tudi prevalenca okužb s HCV v splošnem prebivalstvu v rodni starosti relativno nizka. Zaključujem, da bi bilo v epidemiološko spremljanje hepatitisa C v Sloveniji smiselno vključiti na pet let ponavljajoče se presečne raziskave za ocenjevanje prevalence okužbe s HCV v priložnostnih vzorcih serumov nosečnic, ki so odvzeti za namene presejanja na sifilis.

• Language: Slovenian
• Keywords: Hepatitis C virus, prevalenca, nosečnice
• Work type: Doctoral dissertation
• Organization: MF - Faculty of Medicine
• Year: 2019
• PID: 20.500.12556/RUL-106813
• COBISS.SI-ID: 3969044
• Publication date in RUL: 18.03.2019

Secondary language

• Language: English
• Title: MONITORING INFECTION WITH HEPATITIS C VIRUS AMONG SLOVENIAN PREGNANT WOMEN

Abstract

Aim: Our aim was to assess changes in the prevalence of infection with hepatitis C virus (HCV) during the 15-years period with the methodology of repeated cross sectional studies with unlinked anonymous testing of residual sera, obtained from pregnant women in the largest sample of pregnant women ever. To infer about the prevalence of HCV infection and changing of the prevalence among women of reproductive age, the results were compared with the prevalence among female blood donors of the same age. Objectives and hypotheses: Our objective was to assess the prevalence of HCV infection among Slovenian pregnant women and to describe the changes of this prevalence with repeated cross-sectional studies during the period 1999-2013 and compare the results with the prevalence among Slovenian female blood donors. We tested the following hypotheses: (a) the prevalence of HCV infection among Slovenian pregnant women gradually decreased from 1999 to 2013; (b) the prevalence of HCV infection among Slovenian pregnant women aged 20-29 years in 1999, 2003, 2009 and 2013 was higher than the prevalence among Slovenian blood donors aged 20-29 years. Justification: There were no data about the prevalence of HCV infection and its change through time in the general population of Slovenia. In many countries, the prevalence of HCV infection was assessed in convenience samples of pregnant women. According to available data, no one has ever assessed the changes of the prevalence among pregnant women. Methods: We introduced the method of repeated cross-sectional studies to monitor the change in the prevalence of HCV infection with unlinked anonymous testing of residual sera collected for the purpose of screening pregnant women for syphilis. We used sera from the sera bank of the National Institute of Public Health, which were collected in 1999, 2003, 2009 and 2013 within the network of laboratories performing syphilis testing, for the purpose of epidemiological monitoring of the change in the prevalence of HIV infection with unlinked anonymous testing. Samples were tested for anti-HCV. All anti-HCV reactive samples were tested for HCV RNA and genotypes were determined. Descriptive statistical methods were used to describe the prevalence of HCV infection in pregnant women of different ages in those years and results for 20-29 years old pregnant women were compared with prevalence estimates for female blood donors of the same age. Results: Among the 31,849 tested samples, 41 were anti-HCV positive (0.13 %; 95 % confidence interval (CI): 0.09 % - 0.17 %) and 29 HCV RNA positive (0.09 %; 95% CI: 0.06 % - 0.13 %). The estimates of the annual prevalence of HCV infection (prevalence of HCV RNA) ranged between 0.06 % (95 % CI: 0.02 % - 0.14 %) and 0.14 % (95 % CI: 0.07 % - 0.25 %) (p>0.05). Thus, I did not confirm the hypothesis that the prevalence of HCV infection among Slovenian pregnant women gradually decreased from 1999 to 2013. Also, among the age groups (less than 20 years, 20-29 years and 30 years or more) there were no differences in these years (p>0.05). In 2003, 2009 and 2013, the prevalence of HCV infection among Slovenian blood donors in the age group 20-29 years was 0% (one-sided, 97.5 % CI: 0.00 % - 0.06 %). For these same years, prevalence of HCV infection among Slovenian pregnant women aged 20-29 years was 0.11 % (95% CI: 0.06 % - 0.18 %). I confirmed the hypothesis that the prevalence of HCV infection among Slovenian pregnant women aged 20-29 years in 2003, 2009 and 2013 was higher than the prevalence of HCV infection among female Slovenian blood donors aged 20-29 years. Discussion and conclusion: Within the largest sample of pregnant women in the world and for the longest monitoring period (15 years), we obtained for the first time ever information about the prevalence of HCV infection among Slovenian pregnant women with the introduction of a new and cost-effective method for epidemiological monitoring with repeated cross-sectional studies with unlinked anonymous testing for HCV infection in easily accessible convenience samples of pregnant women. The estimated prevalence was lower than any previously published estimate of the prevalence of HCV infection among pregnant women in European countries and did not change significantly during this period observed. In Slovenia, oportunistic screening of pregnant women for HCV can not be recommended. Pregnant women constitute a more appropriate group of women of childbearing age to infer about the prevalence of HCV infection and its change among women in the general population than female blood donors of the same age. On the basis of these results, we can conclude that prevalence of HCV infections in the general population of childbearing age is relatively low. I conclude that it would be appropriate to include repeated cross-sectional surveys performed every five years to assess the prevalence of HCV infection in convenience samples of sera collected in convenience samples of pregnant women screened for syphilis into the surveillance of hepatitis C in Slovenia.

• Keywords: Hepatitis C virus, prevalence, pregnant women