Sümeyra KAYALI, Mehmet YALNIZ, Adnan SEYREK

Kronik Hepatit ve Siroz Tanılı Hastalarda Hepatit E Virüs Enfeksiyonunun Sıklığı

Amaç: Hepatit E virüsü (HEV); Hepeviridae ailesinin Hepevirus cinsinde yer alan bir RNA virüsüdür. HEV enfeksiyonu klinik olarak genellikle çocuklarda asemptomatik, erişkin yaş grubunda ise semptomatik seyreder. Enfekte hayvanların iyi pişmemiş etlerinin tüketilmesi ve kan transfüzyonu ile bulaşabilse de temel bulaş yolu fekal-oral yoldur. Kronik hepatit ve siroz tanılı hastalarda hepatit E enfeksiyonu akut alevlenmeler, akut karaciğer hasarı, dekompansasyon ve ölüm gibi kötü sonuçlara neden olmaktadır. Bu çalışmada kronik hepatit ve siroz tanılı hastalarda HEV seropozitifliği ve HEV RNA’sının gösterilmesi amaçlandı. Gereç ve Yöntem: Çalışmaya 30 otoimmün hepatit, 30 siroz ve 40 kronik HBV tanılı hasta dahil edildi. Bu hastalardan elde edilen serum örneklerinde mikro ELISA ile anti-HEV IgM ve anti-HEV IgG, RT-PCR ile HEV RNA araştırıldı. Bulgular: Otoimmün hepatit grubunda %13 oranında anti-HEV IgM ve anti-HEV IgG pozitifliği görüldü. Siroz grubunda %33 anti-HEV IgM, %50 anti-HEV IgG pozitifliği görüldü. Kronik HBV grubunda ise %7,5 anti-HEV IgM, %17,5 anti-HEV IgG pozitifliği görüldü. Hastaların hiçbirinde HEV RNA saptanamadı. Sonuç: Her üç hasta grubunda da ülkemiz ve ilimizden bildirilen seroprevalans çalışmalarına göre daha yüksek sıklıkta HEV seropozitifliği saptandı. Kronik hepatit ve siroz tanılı hastalarda klinik yaklaşımlarda HEV enfeksiyonu göz ardı edilmemeli ve HEV enfeksiyonunun önlenebilmesi için hastaların temiz içme suyu ve iyi pişmiş et tüketimi açısından bilinçlendirilmesi gerekmektedir.

The Frequency of Hepatitis E Virus Infection in Patients Diagnosed with Chronic Hepatitis and Cirrhosis

Objective: Hepatitis E virus (HEV) is an RNA virus located in the Hepevirus genus of the Hepeviridae family. HEV infection is generally asymptomatic in children and symptomatic in the adult age group in clinic. Although it can be transmitted by consuming undercooked meat of infected animals and blood transfusion, the main transmission route is fecal-oral route. Hepatitis E infection causes adverse outcomes such as acute exacerbations, acute liver damage, decompensation and death in patients diagnosed with chronic hepatitis and cirrhosis. In this study, it was aimed to demonstrate HEV seropositivity and HEV RNA in patients with chronic hepatitis and cirrhosis. Material and Method: Thirty patients with autoimmune hepatitis, 30 cirrhosis and 40 chronic HBV were included in the study. Anti-HEV IgM and anti-HEV IgG were investigated by micro ELISA and HEV RNA was investigated by RT-PCR in serum samples obtained from these patients. Results: In the autoimmune hepatitis group, anti-HEV IgM and anti-HEV IgG positivity was observed with a rate of 13%. In the cirrhosis group, 33% anti-HEV IgM and 50% anti-HEV IgG positivity were observed. In the chronic HBV group, 7.5% anti-HEV IgM and 17.5% anti-HEV IgG positivity were observed. HEV RNA could not be detected in any of the patients. Conclusion: A higher frequency of HEV seropositivity was found in all three patient groups compared to seroprevalence studies reported in our country and province. HEV infection should not be ignored in clinical approaches in patients diagnosed with chronic hepatitis and cirrhosis, and patients should be informed about clean drinking water and well-cooked meat consumption in order to prevent HEV transmission.

PDF

___

1. Kılıç SS, Akbulut A, Felek S, Kalkan A, Akbulut HH. Elazığ ili ve yöresinde Hepatit E prevalansı araştırılması. Fırat Üniversitesi Sağlık Bilimleri Tıp Dergisi 1999; 13: 41-6.
2. Teshale EH, Hu DJ, Holmberg SD. The two faces of hepatitis E virus. Clin Infect Dis 2010; 51: 328- 34.
3. Kamar N, Selves J, Mansuy JM. Hepatitis E virus and chronic hepatitis in organ-transplant recipients. N Engl J Med 2008; 358: 811-17.
4. Kumar AS, Kumar SP, Singh R et al. Hepatitis (HEV) infection in patients with cirrhosis is associated with rapid decompensation and death. J Hepatol 2007; 46: 387-94.
5. Yang H, Wu J, Yuan Y, Huang W, Jia B. Retrospectively seroprevalence study on anti-HEV-IgG antibody in patients with chronic hepatitis or liver cirrhosis in a Chinese teaching hospital. J Med Virol 2019; 91: 437-43.
6. World Health Organization, Hepatitis E. https://www.who.int/news-room/factsheets/ detail/hepatitis-e. 08.04.2022.
7. Kamar N, Dalton HR, Abravanel F, Izopet J. Hepatitis E virus infection. Clin Microbiol Rev 2014; 27: 116-38.
8. İzat A, Memikoğlu OK, Azap A. Ankara bölgesinde sağlıklı bireylerde hepatit E seroprevalansı. Viral Hepatit Derg 2004; 9: 36-40.
9. Eker A, Tansel O, Kunduracılar H, Tokuç B, Yuluǧkural Z, Yüksel P. Hepatitis E virus epidemiology in adult population in Edirne province, Turkey. Mikrobiyol Bul 2009; 43: 251-58.
10. Karslıgil T, Ekşi F, Balcı İ, Belgin R. Bölgemizde A ve E hepatitlerinin seroprevalansı. Viral Hepatit Derg 2003; 8: 155-9.
11. Umashanker R, Chopra S. Hepatitis E virus Infection. http: //www.uptodate.com/contents/hepatitise- virus-infection 19.11.2020.
12. Zhang L, Jiao S, Yang Z et al. Prevalence of hepatitis E virus infection among blood donors in mainland China: a meta-analysis. Transfusion 2017; 57: 248-57.
13. Li P, Liu J, Li Y et al. The global epidemiology of hepatitis E virus infection: A systematic review and meta-analysis. Liver Int 2020; 40: 1516-28.
14. Olcay D, Eyigün CP, Özgüven ŞV et al. Anti-Hev Antibody prevalence in three distinct regions of Turkey and its Relationship with age, education and abortions. Turk J Med Sci 2003; 33-38.
15. Cesur S, Akin K, Doǧaroǧlu I, Birengel S, Balik I. Hepatitis A and hepatitis E seroprevalence in adults in the Ankara area. Mikrobiyol Bul 2002; 36: 79-83.
16. Aydin NN, Ergünay K, Karagül A, Pinar A, Us D. Investigation of the hepatitis e virus seroprevalence in cases admitted to hacettepe university medical faculty hospital. Mikrobiyol Bul. 2015; 49: 554-64.
17. Ertek M, Yazgı H, Yılmaz Ö, Erol S. Erzurum yöresinde hepatit E virüs seroprevalansı. Flora 2003; 8: 65-9.
18. Leblebicioglu H, Ozaras R. Hepatitis E virus infection in Turkey: a systematic review. Ann Clin Microbiol Antimicrob 2018; 17: 17.
19. Riveiro-Barciela M, Rando-Segura A, Barreira- Díaz A et al. Unexpected long-lasting anti-HEV IgM positivity: Is HEV antigen a better serological marker for hepatitis E infection diagnosis? J Viral Hepat 2020; 27: 747-53.
20. McGivern DR, Lin HS, Wang J et al. Prevalence and ımpact of Hepatitis E virus ınfection among persons with chronic Hepatitis B living in the US and Canada. Open Forum Infect Dis 2019; 6: 175.
21. Takahashi M, Kusakai S, Mizuo H et al. Simultaneous detection of immunoglobulin A (IgA) and IgM antibodies against hepatitis E virus (HEV) Is highly specific for diagnosis of acute HEV infection. J Clin Microbiol 2005; 43: 49-56.
22. Moss da Silva C, Oliveira JM, Mendoza-Sassi RA et al. Detection and characterization of hepatitis E virus genotype 3 in HIV-infected patients and blood donors from southern Brazil. Int J Infect Dis 2019; 86: 114-21.
23. Khuroo MS, Khuroo MS, Khuroo NS. Hepatitis E: Discovery, global impact, control and cure. World J Gastroenterol 2016; 22: 7030-45.
24. Eder M, Strassl R, Beinhardt S et al. High seroprevalence of anti-Hepatitis E antibodies in Austrian patients with autoimmune hepatitis. Liver Int 2019; 39: 640-5.
25. Van Gerven NM, Van der Eijk AA, Pas SD et al. Dutch autoimmune Hepatitis study group. Seroprevalence of Hepatitis E Virus in autoimmune Hepatitis patients in the Netherlands. J Gastrointestin Liver Dis 2016; 25: 9-13.
26. Pischke S, Gisa A, Suneetha PV et al. Increased HEV seroprevalence in patients with autoimmune hepatitis. PLoS One 2014; 9: e85330.
27. Jardi R, Crespo M, Homs M et al. HIV, HEV and cirrhosis: evidence of a possible link from eastern Spain. HIV Med 2012; 13: 379-83.
28. Akyuz F, Cavus B, Pınarbası B et al. Cryptogenic liver cirrhosis and hepatitis E virus (HEV): Are they related? Ann Hepatol 2019; 18: 585-9.
29. Albillos A, Lario M, Álvarez-Mon M. Cirrhosisassociated immune dysfunction: distinctive features and clinical relevance. J Hepato 2014; 61: 1385-96.
30. Nasir M, Wu GY. HEV and HBV Dual infection: A review. J Clin Transl Hepatol 2020; 8: 313-21.
31. Fantilli AC, Trinks J, Marciano S. Unexpected high seroprevalence of hepatitis E virus in patients with alcohol-related cirrhosis. PLoS One 2019; 14: e0224404.
32. Kilonzo SB, Wang YL, Jiang QQ et al. Superinfective Hepatitis E Virus Infection Aggravates Hepatocytes Injury in Chronic Hepatitis B. Curr Med Sci 2019; 39: 719-26.
33. Hoan NX, Tong HV, Hecht N et al. Hepatitis E Virus Superinfection and Clinical Progression in Hepatitis B Patients. EBioMedicine 2015; 2: 2080- 6.
34. Zhang L, Jiang Z, Lv J et al. Comparison of hepatitis E virus seroprevalence between HBsAgpositive population and healthy controls in Shandong province, China. BMC Infect Dis 2018; 18: 75.
35. Bayram A, Eksi F, Mehli M, Sözen E. Prevalence of hepatitis E virus antibodies in patients with chronic hepatitis B and chronic hepatitis C. Intervirology 2007; 50: 281-6.
36. Löve A, Björnsdottir TB, Olafsson S, Björnsson ES. Low prevalence of hepatitis E in Iceland: a seroepidemiological study. Scand J Gastroenterol 2018; 53: 293-6.
37. Taherkhani R, Makvandi M, Farshadpour F. Development of enzyme-linked immunosorbent assays using 2 truncated ORF2 proteins for detection of IgG antibodies against hepatitis E virus. Ann Lab Med 2014; 34: 118-26.
38. Avellon A, Morago L, Garcia-Galera del Carmen M, Munoz M, Echevarría JM. Comparative sensitivity of commercial tests for hepatitis E genotype 3 virus antibody detection. J Med Virol 2015; 87: 1934-9.
39. Abravanel F, Goutagny N, Perret C et al. Evaluation of two VIDAS ®prototypes for detecting anti- HEV IgG. J Clin Virol 2017; 89: 46-50.
40. Llovet LP, Gratacós-Ginés J, Ortiz O et al. Higher seroprevalence of hepatitis E virus in autoimmune hepatitis: Role of false-positive antibodies. Liver Int 2020; 40: 558-64.
41. Yaşar O, Karatayli E, Cengiz G et al. HEV seroprevalence in blood donors in Turkey by two commercial total anti-HEV Ab ELISA kits. J Med Virol 2019; 91: 2174-81.
42. Lapa D, Brega C, Mammone A, Zaccarelli M, Capobianchi MR, Garbuglia AR. Diagnostic performance of hepatitis E virus antigen assay in hepatitis E virus acute infection. New Microbiol 2016; 40: 246-50.
43. Choi Y, Zhang X, Skinner B. Analysis of IgG Anti-HEV Antibody protective levels during Hepatitis E Virus reinfection in experimentally infected rhesus macaques. J Infect Dis 2019; 219: 916- 24.
44. Servant-Delmas A, Abravanel F, Lefrère JJ et al. New insights into the natural history of hepatitis E virus infection through a longitudinal study of multitransfused immunocompetent patients in France. J Viral Hepat 2016; 23: 569-75.