Derleme


DOI :10.18017/iuitfd.330044   IUP :10.18017/iuitfd.330044    Tam Metin (PDF)

OKÜLT HEPATİT B VİRUS ENFEKSİYONU: MOLEKÜLER MEKANİZMALAR VE KLİNİK ÖNEMİ

Bülent Çakal

Okült Hepatitis B Virüs (HBV) infeksiyonu (OBİ) serum HBV DNA statüsü dikkate alınmaksızın mevcut serolojik testler ile HBV yüzey antijeni (HBsAg) negatif tespit edilen bireylerin karaciğerin de HBV genomunun uzun süreli persistan varlığı olarak tanımlanır. OBİ virüse ve infekte bireye ait faktörler ile çevresel faktörlerin zemininde gelişen genetik, epigenetik ve immünolojik mekanizmaların karşılıklı etkileşimi ile şekillenen, HBV infeksiyonunun doğal seyri içerisinde yer alan muhtemel safhalarından biri olarak kabul edilir. OBİ klinik açıdan; okült virüsün kan transfüzyonu, doğum, hemodiyaliz ve ortotopik karaciğer gibi organ nakli yolu ile bulaşını takiben alıcıda tipik yeni HBV infeksiyonuna neden olabilmesi, immünsüpresyon koşullarında OBİ reaktivasyonu ve takiben HBV ilişkili (akut ve fulminan hepatit) karaciğer hastalıkları, kronik karaciğer hastalıklarının (KKH) progresyonu üzerine etkisi ile özellikle hepatoselüler karsinoma (HSK) için artan bir risk faktörü olduğu yönünde hipotez uyarınca yoğun bir tartışma ve araştırma konusudur. Buna karşın gerek HBV infeksiyonunun bu özgün formuna neden olan gerekse ilişkili olduğu karaciğer hastalıklarının patogenezinde rol alan moleküler mekanizmalar henüz tam olarak aydınlatılamamıştır. Bu derlemede OBİ’nin klinik önemi, epidemiyolojik özellikleri ve laboratuar tanısına yönelik bilimsel literatürün gözden geçirilmesi amaçlanmıştır.

DOI :10.18017/iuitfd.330044   IUP :10.18017/iuitfd.330044    Tam Metin (PDF)

OCCULT HEPATITIS B VIRUS INFECTION: MOLECULAR MECHANISMS AND CLINICAL SIGNIFICANCE

Bülent Çakal

Occult Hepatitis B Virus (HBV) infection (OBI) is defined as the long-lasting persistence of HBV genomes in the hepatocytes of individuals testing negative for HBV surface antigen (HBsAg) by currently available assays and usually for serum HBV DNA. OBI is considered as the possible phase in the natural history of chronic HBV infection that the host’s immune surveillance and epigenetic mechanisms are likely involved. Clinical impact of OB is that it can be transmitted (i.e., through blood transfusion, by liver organ transplantation, hemodialysis and parturition) causing classic forms of hepatitis B in newly infected individuals. The development of an immunosuppressive status may induce OBI reactivation and development of acute and often severe hepatitis. OBI can favor the progression of liver fibrosis. Also OBİ infection has been hypothesized to be a significant risk factor contributing to the progression of chronic liver diseases (CLD) with increased risk for hepatocellular carcinoma (HCC) which may lead to an increased progression of liver diseases. Although OBI is considered a phase in the natural history of HBV, the molecular mechanisms leading to its occurrence and its contribution to HCC development are yet poorly understood. In this review, it is aimed to examine clinical importance, epidemiological aspects and laboratory diagnosis of OBI in recent literature.


PDF Görünüm

Referanslar

  • 1. World Health Organization. http://www.who.int/mediacentre/factsheets/fs204/en/ erişim 12 Ocak 2015. google scholar
  • 2. World Health Organization. http://www.who.int/mediacentre/factsheets/fs297/en/ erişim 12 Ocak 2015. google scholar
  • 3. Shi J, Zhu L, Liu S, Xie WF. A Metaanalysis of case-control studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma in China. Br J Cancer 2005;92:607–12. google scholar
  • 4. Chang MH. Cancer prevention by vaccination against hepatitis B. Recent Results. Cancer Res 2009; 181: 85-94. google scholar
  • 5. Kew MC. Epidemiology of hepatocellular carcinoma. Toxicology 2002; 181–182: 35–8. google scholar
  • 6. Lai CL, Ratziu V, Yuen MF, Poynard T. Viral hepatitis B. Lancet 2003; 62: 2089–94. google scholar
  • 7. Ganem D, Prince AM. Hepatitis B virus infection natural history and clinical consequences. N Engl J Med 2004;350: 1118–29. google scholar
  • 8. Fattovich G, Giustina G, Sanchez-Tapias J, Quero C, Mas A, et al. Delayed clearance of serum HBsAg in compensated cirrhosis B: relation to interferon alpha therapy and disease prognosis. European Concerted Action on Viral Hepatitis (EUROHEP). Am J Gastroenterol 1998; 93: 896–900. google scholar
  • 9. Raimondo G, Allain JP, Brunetto MR, Buendia MA, Chen DS, Colombo M, et al. Statements from the Taormina expert meeting on occult hepatitis B virus infection. J Hepatol 2008; 49: 652-7. google scholar
  • 10. Torbenson M, Thomas DL. Occult hepatitis B. Lancet Infect Dis. 2002; 2: 479-86. google scholar
  • 11. Pollicino T, Saitta C. Occult hepatitis B virus and hepatocellular carcinoma. World J Gastroenterol 2014; 20(20): 5951-61. google scholar
  • 12. Samal J, Kandpal M, Vivekanandan P. Molecular mechanisms underlying occult hepatitis B virus infection. Clin Microbiol Rev 2012;25:142-63. google scholar
  • 13. Raimondo G, Pollicino T, Cacciola I, Squadrito G. Occult hepatitis B virus infection. J Hepatol 2007; 46:160–70. google scholar
  • 14. Fang Y, Shang QL, Liu JY, Li D, Xu WZ, Teng X, et al. Prevalence of occult hepatitis B virus infection among hepatopathy patients and healthy people in China. J Infect 2009; 58: 383–8. google scholar
  • 15. Brechot C, Thiers V, Kremsdorf D, Nalpas B, Pol S, Paterlini-Br_echot P. Persistent hepatitis B virus infection in subjects without hepatitis B surface antigen: clinically significant or purely “occult”? Hepatology 2001;34: 94–203. google scholar
  • 16. Ohba K, Kubo S, Tamori A, Hirohashi K, Tanaka H, Shuto T, et al. Previous or occult hepatitis B virus infection in hepatitis B surface antigen negative and anti-hepatitis C negative patients with hepatocellular carcinoma. Surg Today 2004; 34: 842–8. google scholar
  • 17. Pollicino T, Saitta C, Raimondo G. Hepatocellular carcinoma: the point of view of the hepatitis B virus. Carcinogenesis 2011; 32: 1122-32. google scholar
  • 18. Raimondo G, Caccamo G, Filomia R, Pollicino T. Occult HBV infection. Semin Immunopathol 2013; 35: 9-52. google scholar
  • 19. Larrubia JR. Occult hepatitis B virus infection: a complex entity with relevant clinical implications. World J Gastroenterol 2011; 17: 1529-30. google scholar
  • 20. Mrani S, Chemin I, Menouar K, Guillaud O, Pradat P, Borghi G, et al. Occult HBV infection may represent a major risk factor of non-response to antiviral therapy of chronic hepatitis C. J Med Virol 2007; 79: 1075–81. google scholar
  • 21. De Mitri MS, Cassini R, Bernardi M. Hepatitis B virus-related hepatocarcinogenesis: molecular oncogenic potential of clear or occult infections. Eur J Cancer 2010; 46: 2178–86. google scholar
  • 22. Chemin I, Trepo C. Clinical impact of occult HBV infections. J Clin Virol 2005; 34: 15–21. google scholar
  • 23. De la Fuente RA, Gutiérrez ML, Garcia-Samaniego J, Fernández-Rodriguez C, Lledó JL, Castellano G. Pathogenesis of occult chronic hepatitis B virus infection. World J Gastroenterol 2011; 17: 1543-8. google scholar
  • 24. Hassan ZK, Hafez MM, Mansor TM, Zekri AR. Occult HBV infection among Egyptian hepatocellular carcinoma patients. Virol. J 2011; 8: 90-5. google scholar
  • 25. Lalazar G, Rund D, Shouval D. Screening, prevention and treatment of viral hepatitis B reactivation in patients with haematological malignancies. Br J Haematol 2007; 136: 699-712. google scholar
  • 26. Hollinger FB. Hepatitis B virus infection and transfusion medicine: science and the occult. Transfusion 2008; 48: 1001-26. google scholar
  • 27. Cheung CK, Lo CM, Man K, Lau GK. Occult hepatitis B virus infection of donor and recipient origin after liver transplantation despite nucleoside analogue prophylaxis. Liver Transpl 2010; 16: 1314-23. google scholar
  • 28. Allain JP, Cox L. Challenges in hepatitis B detection among blood donors. Curr Opin Hematol 2011; 18: 461-6. google scholar
  • 29. Teresa Pollicino, Giovanni Raimondo. Occult Hepatitis B Infection. Journal of Hepatology 2014. 61:688–9. google scholar
  • 30. Mason AL, Xu L, Guo L, Kuhns M, Perrillo RP. Molecular basis for persistent hepatitis B virus infection in the liver after clearance of serum hepatitis B surface antigen. Hepatology 1998; 27: 1736-42. google scholar
  • 31. Zoulim F. New insight on hepatitis B virus persistence from the study of intrahepatic viral cccDNA. J Hepatol 2005; 42: 302–8. google scholar
  • 32. R. A. A. Pondé Molecular mechanisms underlying HBsAg negativity in occult HBV infection. Eur J Clin Microbiol Infect Dis. 2015; 34: 1709–31. google scholar
  • 33. Conjeevaram HS, Lok AS. Occult hepatitis B virus infection: a hidden menace? Hepatology 2001; 34: 204-6. google scholar
  • 34. Minuk GY, Sun DF, Uhanova J, Zhang M, Caouette S, Nicolle LE, et al. Occult hepatitis B virus infection in a North American community-based population. J Hepatol 2005; 42: 480–5. google scholar
  • 35. Kim SM, Lee KS, Park CJ, Lee JY, Kim KH, Park JY, et al. Prevalence of occult HBV infection among subjects with normal serum ALT levels in Korea. J Infect 2007; 54: 185–91. google scholar
  • 36. Hui CK, Sun J, Au WY, Lie AK, Yueng YH, Zhang HY, et al. Occult hepatitis B virus infection in hematopoietic stem cell donors in a hepatitis B virus endemic area. J Hepatol 2005; 42: 813–9. google scholar
  • 37. Zhang Z, Zhang L, Dai Y, Jin L, Sun B, Su Q, Li X . Occult hepatitis B virus infection among people with a family history of chronic hepatitis B virus infection J Med Virol 2015; 87(11): 1890-8. google scholar
  • 38. Raimondo G, Navarra G, Mondello S, Costantino L, Colloredo G, Cucinotta E, et al. Occult hepatitis B virus in liver tissue of individuals without hepatic disease. J Hepatol 2008;48: 743–6. google scholar
  • 39. Stramer SL, Wend U, Candotti D, Foster GA, Hollinger FB, Dodd RY, et al. Nucleic acid testing to detect HBV infection in blood donors. N Engl J Med 2011; 364: 236–47. google scholar
  • 40. Oluyinka OO, Tong HV, Bui Tien S, Fagbami AH, Adekanle O, Ojurongbe O, et al. Occult Hepatitis B Virus Infection in Nigerian Blood Donors and Hepatitis B Virus Transmission Risks. PLOS ONE 2015; 6;10(7):e0131912. google scholar
  • 41. Candotti D, Lin CK, Belkhiri D, Sakuldamrongpanich T, Biswas S, Lin S, et al. Occult hepatitis B infection in blood donors from South East Asia: molecular characterisation and potential mechanisms of occurrence. Gut 2012; 61(12): 1744-53. google scholar
  • 42. Song EY, Yun YM, Park MH, Seo DH. Prevalence of occult hepatitis B virus infection in a general adult population in Korea. Intervirology 2009; 52: 57–62. google scholar
  • 43. Yuen MF, Lee CK, Wong DK, Fung J, Hung I, Hsu A et al. Prevalence of occult hepatitis B infection in a highly endemic area for chronic hepatitis B: a study of a large blood donor population. Gut 2010; 59(10): 1389-93. google scholar
  • 44. Nna E, Mbamalu C, Ekejindu I (2014) Occult hepatitis B viral infection among blood donors in South- Eastern Nigeria. Pathog Glob Health 2014; 108: 223–8 google scholar
  • 45. Jutavijittum P, Andernach IE, Yousukh A, Samountry B, Samountry K, Thammavong T, et al. Occult hepatitis B infections among blood donors in Lao PDR. Vox Sang 2014; 106: 31–37. google scholar
  • 46. O’Brien SF, Fearon MA, Yi QL, Fan W, Scalia V, Muntz IR, Vamvakas EC. Hepatitis B virus DNA-positive, hepatitis B surface antigen-negative blood donations intercepted by anti-hepatitis B core antigen testing: the Canadian Blood Services experience. Transfusion 2007; 47: 1809-15. google scholar
  • 47. Hofer M, Joller-Jemelka HI, Grob PJ, Lüthy R, Opravil M. Frequent chronic hepatitis B virus infection in HIV-infected patients positive for antibody to hepatitis B core antigen only. Swiss HIV Cohort Study. Eur J Clin Microbiol Infect Dis 1998; 17: 6-13. google scholar
  • 48. Núñez M, Ríos P, Pérez-Olmeda M, Soriano V. Lack of ‘occult’ hepatitis B virus infection in HIV-infected patients. AIDS 2002; 16: 2099-101. google scholar
  • 49. Torbenson M, Kannangai R, Astemborski J, Strathdee SA, Vlahov D, Thomas DL. High prevalence of occult hepatitis B in Baltimore injection drug users. Hepatology 2004; 39: 51–7. google scholar
  • 50. Toyoda H, Hayashi K, Murakami Y, Honda T, Katano Y, Nakano I, et al. Prevalence and clinical implications of occult hepatitis B viral infection in hemophilia patients in Japan. J Med Virol 2004; 73: 195–9. google scholar
  • 51. Wong DK, Huang FY, Lai CL, Poon RT, Seto WK, Fung J, et al. Occult hepatitis B infection and HBV replicative activity in patients with cryptogenic cause of hepatocellular carcinoma. Hepatology 2011; 54: 829–36. google scholar
  • 52. Raffa G, Maimone S, Cargnel A, Santantonio T, Antonucci G, Massari M, et al. Analysis of occult hepatitis B virus infection in liver tissue of HIV patients with chronic hepatitis C. AIDS 2007; 21: 2171–5. google scholar
  • 53. Fabrizi F, Messa PG, Lunghi G, Aucella F, Bisegna S, Mangano S, et al. Occult hepatitis B virus infection in dialysis patients: a multicentre survey. Aliment Pharmacol Ther 2005; 21: 1341–47. google scholar
  • 54. Minuk GY, Sun DF, Greenberg R, Zhang M, Hawkins K, Uhanova J, et al. Occult hepatitis B virus infection in a North American adult hemodialysis patient population. Hepatology 2004; 40: 1072-77. google scholar
  • 55. Chan HL, Tsang SW, Leung NW, Tse CH, Hui Y, Tam JS, et al. Occult HBV infection in cryptogenic liver cirrhosis in an area with high prevalence of HBV infection. Am J Gastroenterol 2002; 97: 1211-15. google scholar
  • 56. Shetty K, HussainM, Nei L, Reddy KR, Lok AS. Prevalence and significance of occult hepatitis B in a liver transplant population with chronic hepatitis C. Liver Transpl 2008; 14: 534–40. google scholar
  • 57. Allain JP, Candotti D. Diagnostic algorithm for HBV safe transfusion. Blood Transfus 2009; 7: 174–82. google scholar
  • 58. Chemin I, Guillaud O, Queyron PC, Trepo C. Close monitoring of serum HBV DNA levels and liver enzymes levels is most useful in the management of patients with occult HBV infection. J Hepatol 2009; 51: 824–5. google scholar
  • 59. Allain JP and Laura Cox Challenges in hepatitis B detection among blood donors Curr Opin Hematol 2011; 18: 461–6. google scholar
  • 60. Komiya Y, Katayama K, Yugi H, Mizui M, Matsukura H, Tomoguri T, et al. Minimum infectious dose of hepatitis B virus in chimpanzees and difference in the dynamics of viremia between genotype A and genotype C. Transfusion 2008; 48: 286–94. google scholar
  • 61. Allain JP, Belkhiri D, Vermeulen M, Crookes R, Cable R, Amiri A, et al. R) Characterization of occult hepatitis B virus strains in South African blood donors. Hepatology 2009; 49: 1868–76. google scholar
  • 62. Prati D, Gerosa A, Porretti L. Occult HBV infection and blood transfusion. Journal of Hepatology 2006; 44: 818. google scholar
  • 63. Cholongitas E, Papatheodoridis GV, Burroughs AK. Liver grafts from anti-hepatitis B core positive donors: a systematic review. J Hepatol 2010; 52: 272–9. google scholar
  • 64. Coffin CS, Mulrooney-Cousins PM, van MG, Roberts JP, Michalak TI, Terrault NA. Hepatitis B virus quasispecies in hepatic and extrahepatic viral reservoirs in liver transplant recipients on prophylactic therapy. Liver Transpl 2011; 17: 955–62. google scholar
  • 65. Toniutto P, Minisini R, Fabris C, De FT, Marangoni F, Burlone M, et al. Occult hepatitis B virus infection in liver transplant recipients with recurrent hepatitis C: relationship with donor age and fibrosis progression. Clin Transplant 2011; 23: 184–90. google scholar
  • 66. Sagnelli E, Pisaturo M, Martini S, Filippini P, Sagnelli C, Coppola N. Clinical impact of occult hepatitis B virus infection in immunosuppressed patients. World J Hepatol 2014; 6: 384-93. google scholar
  • 67. Yeo W, Chan TC, Leung NW, Lam WY, Mo FK, Chu MT, et al. Hepatitis B virus reactivation in lymphoma patients with prior resolved hepatitis B undergoing anticancer therapy with or without rituximab. J Clin Oncol 2009; 27: 605–11. google scholar
  • 68. Pei SN, Chen CH, Lee CM, Wang MC, Ma MC, Hu TH, et al. Reactivation of hepatitis B virus following rituximabbased regimens: a serious complication in both HBsAg-positive and HBsAg-negative patients. Ann Hematol 2010; 89: 255–62. google scholar
  • 69. Ritchie D, Piekarz RL, Blombery P, Karai LJ, Pittaluga S, Jaffe ES, et al. Reactivation of DNA viruses in association with histone deacetylase inhibitor therapy: a case series report. Haematologica 2009; 94: 1618–22. google scholar
  • 70. Onozawa M, Hashino S, Izumiyama K, Kahata K, Chuma M, Mori A, et al. Progressive disappearance of anti-hepatitis B surface antigen antibody and reverse seroconversion after allogeneic hematopoietic stem cell transplantation in patients with previous hepatitis B virus infection. Transplantation 2005; 79: 616–9. google scholar
  • 71. Vigano M, Vener C, Lampertico P, Annaloro C, Pichoud C, Zoulim F, et al. Risk of hepatitis B surface antigen seroreversion after allogeneic hematopoietic SCT. Bone Marrow Transplant 2011; 46: 125–31. google scholar
  • 72. EASL clinical practice guidelines: management of chronic hepatitis B. J Hepatol 2012; 57: 167–185. google scholar
  • 73. Covolo L, Pollicino T, Raimondo G, Donato F. Occult hepatiti B virus and risk for chronic liver disease: A meta-analysis. Dig Liv Dis 2013; 45: 238–44. google scholar
  • 74. Shi Y, Wu YH, Wu W, Zhang WJ, Yang J, Chen Z. Association between occult hepatitis B virus infection and the risk of hepatocellular carcinoma: a meta-analysis. Liver Int 2012; 32: 231–40. google scholar
  • 75. Squadrito G, Spinella R, Raimondo G. The clinical significance of occult HBV infection Annals of Gastroenterology 2014; 27: 15-9. google scholar
  • 76. Murakami Y, Saigo K, Takashima H, Minami M, Okanoue T, Bréchot C, Paterlini-Bréchot P. Large scaled analysis of hepatitis B virus (HBV) DNA integration in HBV related hepatocellular carcinomas. Gut 2005; 54: 1162–8. google scholar
  • 77. Pollicino T, Squadrito G, Cerenzia G, Cacciola I, Raffa G, Craxi A, et al. Hepatitis B virus maintains its pro-oncogenic properties in the case of occult HBV infection. Gastroenterology 2004; 126: 102-10. google scholar
  • 78. Wong DK, Yuen MF, Poon RT, Yuen JC, Fung J, Lai CL. Quantification of hepatitis B virus covalently closed circular DNA in patients with hepatocellular carcinoma. J Hepatol 2006; 45: 553-9. google scholar
  • 79. Sheu JC, Huang GT, Shih LN, Lee WC, Chou HC, Wang JT, et al. Hepatitis C and B viruses in hepatitis B surface antigen-negative hepatocellular carcinoma. Gastroenterology 1992; 103: 1322-1327. google scholar
  • 80. Paterlini P, Driss F, Nalpas B, Pisi E, Franco D, Berthelot P, et al. Persistence of hepatitis B and hepatitis C viral genomes in primary liver cancers from HBsAg-negative patients: a study of a low-endemic area. Hepatology 1993; 17: 20-9. google scholar
  • 81. Yu MC, Yuan JM, Ross RK, Govindarajan S. Presence of antibodies to the hepatitis B surface antigen is associated with an excess risk for hepatocellular carcinoma among non-Asians in Los Angeles County, California. Hepatology 1997; 25:226-8. google scholar
  • 82. Bläckberg J, Kidd-Ljunggren K. Occult hepatitis B virus after acute self-limited infection persisting for 30 years without sequence variation. J Hepatol 2000; 33: 992-7. google scholar
  • 83. Yuki N, Nagaoka T, Yamashiro M, Mochizuki K, Kaneko A, Yamamoto K, et al. Long-term histologic and virologic outcomes of acute self-limited hepatitis B. Hepatology 2003; 37: 1172-9. google scholar
  • 84. Mulrooney-Cousins PM, Michalak TI. Persistent occult hepatitis B virus infection: experimental findings and clinical implications. World J Gastroenterol 2007; 13: 5682-6. google scholar
  • 85. Wong D. K.-H., Fung J., Lee C.-K., Seto W.-K., Leung J.,. Yuen M.-F et.al. Intrahepatic hepatitis B virus replication and liver histology in subjects with occult hepatitis B infection. Clin Microbiol Infect 2016; 22: 290. google scholar
  • 86. Kannangai R, Vivekanandan P, Netski D, Mehta S, Kirk GD, Thomas DL, et al. Liver enzyme flares and occult hepatitis B in persons with chronic hepatitis C infection. J Clin Virol 2007; 39: 101–5. google scholar
  • 87. Raimondo G, Pollicino T, Squadrito G. What is the clinical impact of occult hepatitis B virus infection? Lancet 2005; 365: 638-40. google scholar
  • 88. Brechot C. Pathogenesis of hepatitis B virus-related hepatocellular carcinoma: old and new paradigms. Gastroenterology 2004; 127: 56–61. google scholar
  • 89. Beasley RP. Hepatitis B virus. The major etiology of hepatocellular carcinoma. Cancer 1988; 61: 1942-56. google scholar
  • 90. Kao JH, Chen PJ, Lai MY, Chen DS. Occult hepatitis B virüs infection and clinical outcomes of patients with chronic hepatitis C. J. Clin. Microbiol 2002, 40: 4068–71. google scholar
  • 91. Koike K, Shimotouno K, Okada S, Okamoto H, Hayashi N, Ueda K, et al. Survey of hepatitis B virus coinfection in hepatitis C virus-infected patients suffering from chronic hepatitis and hepatocellular carcinoma in Japan. Jpn J Cancer Res 1999; 90: 1270-2. google scholar
  • 92. Yotsuyanagi H, Hashidume K, Suzuki M, Maeyama S, Takayama T, Uchikoshi T. Role of hepatitis B virus in hepatocarcinogenesis in alcoholics. Alcohol Clin Exp Res 2004; 28: 181-5. google scholar
  • 93. Chung HT, Lai CL, Wu PC, Lok AS. Synergism of chronicalcoholism and hepatitis B infection in liver disease. J Gastroenterol Hepatol 1989; 4: 11-6. google scholar
  • 94. Lok AS, Everhart JE, Di Bisceglie AM, Kim HY, Hussain M,Morgan TR. Occult and previous hepatitis B virus infection are not associated with hepatocellular carcinoma in United States patients with chronic hepatitis C. Hepatology 2011; 54: 434-42. google scholar
  • 95. Chen YC, Sheen IS, Chu CM, Liaw YF. Prognosis following spontaneous HBsAg seroclearance in chronic hepatitis B patients with or without concurrent infection. Gastroenterology 2002; 123: 1084-9. google scholar
  • 96. Fwu CW, Chien YC, Kirk GD, Nelson KE, You SL, Kuo HS, Feinleib M, Chen CJ. Hepatitis B virus infection and hepatocellular carcinoma among parous Taiwanese women: nationwide cohort study. J Natl Cancer Inst 2009; 101: 1019-27. google scholar
  • 97. Werle-Lapostolle B, Bowden S, Locarnini S, Wursthorn K, Petersen J, Lau G, et al. Persistence of cccDNA during the natural history of chronic hepatitis B and decline during adefovir dipivoxil therapy. Gastroenterology 2004; 126: 1750-8. google scholar
  • 98. Korba BE, Wells FV, Baldwin B, Cote PJ, Tennant BC, Popper H, et al. Hepatocellular carcinoma in woodchuck hepatitis virusinfected woodchucks: presence of viral DNA in tumor tissue from chronic carriers and animals serologically recovered from acute infections. Hepatology 1989; 9: 461–70 google scholar
  • 99. Marion,P.I. In: McLachlan,A. (ed) Molecular Biology of Hepatitis B Virus. CRC Press, Boca Raton, FL, 1991; 39–51. google scholar
  • 100. Michalak TI, Pardoe IU, Coffin CS, Churchill ND, Freake DS, Smith P, et al. Occult lifelong persistence of infectious hepadnavirus and residual liver inflammation in woodchucks convalescent from acute viral hepatitis. Hepatology 1999; 29: 928-38. google scholar
  • 101. Transy C, Fourel G, Robinson WS, Tiollais P, Marion PL, Buendia MA. Frequent amplification of c-myc in ground squirrel liver tumors associated with past or ongoing infection with a hepadnavirus. Proc Natl Acad Sci U S A 1992; 89: 3874-8. google scholar
  • 102. Tanaka M, Tanaka H, Tsukuma H, Ioka A, Oshima A, Nakahara T. Risk factors for intrahepatic cholangiocarcinoma: a possible role of hepatitis B virus. J Viral Hepat 2010; 17: 742–8. google scholar
  • 103. Perumal V, Wang J, Thuluvath P, Choti M, Torbenson M. Hepatitis C and hepatitis B nucleic acids are present in intrahepatic cholangiocarcinomas from the United States. Hum Pathol 2006; 37: 1211–6. google scholar
  • 104. Shafritz DA, Shouval D, Sherman HI, Hadziyannis SJ, Kew MC. Integration of hepatitis B virus DNA into the genome of liver cells in chronic liver disease and hepatocellular carcinoma. Studies in percutaneous liver biopsies and post-mortem tissue specimens. N Engl J Med 1981; 305: 1067–73. google scholar
  • 105. Gozuacik D, Murakami Y, Saigo K, Chami M, Mugnier C, Lagorce D, et al. Identification of human cancer-related genes by naturally occurring Hepatitis B Virus DNA tagging. Oncogene 2001; 20: 6233-40. google scholar
  • 106. Makvandi M. Update on occult hepatitis B virus infection. World J Gastroenterol 2016; 22(39): 8720-87. google scholar

Atıflar

Biçimlendirilmiş bir atıfı kopyalayıp yapıştırın veya seçtiğiniz biçimde dışa aktarmak için seçeneklerden birini kullanın


DIŞA AKTAR



APA

Çakal, B. (2017). OKÜLT HEPATİT B VİRUS ENFEKSİYONU: MOLEKÜLER MEKANİZMALAR VE KLİNİK ÖNEMİ. İstanbul Tıp Fakültesi Dergisi, 80(2), 71-81. https://doi.org/10.18017/iuitfd.330044


AMA

Çakal B. OKÜLT HEPATİT B VİRUS ENFEKSİYONU: MOLEKÜLER MEKANİZMALAR VE KLİNİK ÖNEMİ. İstanbul Tıp Fakültesi Dergisi. 2017;80(2):71-81. https://doi.org/10.18017/iuitfd.330044


ABNT

Çakal, B. OKÜLT HEPATİT B VİRUS ENFEKSİYONU: MOLEKÜLER MEKANİZMALAR VE KLİNİK ÖNEMİ. İstanbul Tıp Fakültesi Dergisi, [Publisher Location], v. 80, n. 2, p. 71-81, 2017.


Chicago: Author-Date Style

Çakal, Bülent,. 2017. “OKÜLT HEPATİT B VİRUS ENFEKSİYONU: MOLEKÜLER MEKANİZMALAR VE KLİNİK ÖNEMİ.” İstanbul Tıp Fakültesi Dergisi 80, no. 2: 71-81. https://doi.org/10.18017/iuitfd.330044


Chicago: Humanities Style

Çakal, Bülent,. OKÜLT HEPATİT B VİRUS ENFEKSİYONU: MOLEKÜLER MEKANİZMALAR VE KLİNİK ÖNEMİ.” İstanbul Tıp Fakültesi Dergisi 80, no. 2 (Oct. 2024): 71-81. https://doi.org/10.18017/iuitfd.330044


Harvard: Australian Style

Çakal, B 2017, 'OKÜLT HEPATİT B VİRUS ENFEKSİYONU: MOLEKÜLER MEKANİZMALAR VE KLİNİK ÖNEMİ', İstanbul Tıp Fakültesi Dergisi, vol. 80, no. 2, pp. 71-81, viewed 19 Oct. 2024, https://doi.org/10.18017/iuitfd.330044


Harvard: Author-Date Style

Çakal, B. (2017) ‘OKÜLT HEPATİT B VİRUS ENFEKSİYONU: MOLEKÜLER MEKANİZMALAR VE KLİNİK ÖNEMİ’, İstanbul Tıp Fakültesi Dergisi, 80(2), pp. 71-81. https://doi.org/10.18017/iuitfd.330044 (19 Oct. 2024).


MLA

Çakal, Bülent,. OKÜLT HEPATİT B VİRUS ENFEKSİYONU: MOLEKÜLER MEKANİZMALAR VE KLİNİK ÖNEMİ.” İstanbul Tıp Fakültesi Dergisi, vol. 80, no. 2, 2017, pp. 71-81. [Database Container], https://doi.org/10.18017/iuitfd.330044


Vancouver

Çakal B. OKÜLT HEPATİT B VİRUS ENFEKSİYONU: MOLEKÜLER MEKANİZMALAR VE KLİNİK ÖNEMİ. İstanbul Tıp Fakültesi Dergisi [Internet]. 19 Oct. 2024 [cited 19 Oct. 2024];80(2):71-81. Available from: https://doi.org/10.18017/iuitfd.330044 doi: 10.18017/iuitfd.330044


ISNAD

Çakal, Bülent. OKÜLT HEPATİT B VİRUS ENFEKSİYONU: MOLEKÜLER MEKANİZMALAR VE KLİNİK ÖNEMİ”. İstanbul Tıp Fakültesi Dergisi 80/2 (Oct. 2024): 71-81. https://doi.org/10.18017/iuitfd.330044



ZAMAN ÇİZELGESİ


Gönderim31.07.2016
Kabul31.03.2017
Çevrimiçi Yayınlanma30.06.2017

LİSANS


Attribution-NonCommercial (CC BY-NC)

This license lets others remix, tweak, and build upon your work non-commercially, and although their new works must also acknowledge you and be non-commercial, they don’t have to license their derivative works on the same terms.


PAYLAŞ




İstanbul Üniversitesi Yayınları, uluslararası yayıncılık standartları ve etiğine uygun olarak, yüksek kalitede bilimsel dergi ve kitapların yayınlanmasıyla giderek artan bilimsel bilginin yayılmasına katkıda bulunmayı amaçlamaktadır. İstanbul Üniversitesi Yayınları açık erişimli, ticari olmayan, bilimsel yayıncılığı takip etmektedir.