Korean J Gastroenterol.  2013 Sep;62(3):143-147. 10.4166/kjg.2013.62.3.143.

Definition, Diagnosis, and Prevalence of Occult Hepatitis B Virus Infection

• Kim YS

• KMID: 1707195
• DOI: http://doi.org/10.4166/kjg.2013.62.3.143

Abstract

Occult HBV infection is characterized by the absence of serum HBsAg with persistence of low level of intrahepatic HBV DNA. Several suggested mechanisms for the origin of occult HBV infection include strong suppression of viral replication and gene expression, mutation in the regulatory regions of HBV genome, formation of immunoglobulin-bound HBsAg, viral interference, and blockage of HBsAg secretion from infected hepatocytes. Standardized assays are not yet available, and sensitive HBV DNA amplification assay is necessary for the diagnosis of cryptic infection. Detection rate of HBV DNA is highest in IgG anti-HBc positive population. However, neither anti-HBc nor anti-HBs can be detected in a significant proportion of infected persons. Occult HBV infection occurs in a number of clinical settings and is highly prevalent in HCV-infected patients as well as in patients with cryptogenic chronic liver disease including hepatocellular carcinoma.

Keyword

Occult hepatitis B virus infection

MeSH Terms

DNA, Viral/analysis
Hepatitis B/*diagnosis/*epidemiology/metabolism
Hepatitis B Antibodies/blood
Hepatitis B Core Antigens/immunology
Hepatitis B Surface Antigens/blood
Humans
DNA, Viral
Hepatitis B Antibodies
Hepatitis B Core Antigens
Hepatitis B Surface Antigens

Reference

References

1. Yotsuyanagi H, Yasuda K, Iino S, et al. Persistent viremia after recovery from self-limited acute hepatitis B. Hepatology. 1998; 27:1377–1382.

2. Bläckberg J, Kidd-Ljunggren K. Occult hepatitis B virus after acute self-limited infection persisting for 30 years without sequence variation. J Hepatol. 2000; 33:992–997.

3. Rehermann B, Ferrari C, Pasquinelli C, Chisari FV. The hepatitis B virus persists for decades after patients' recovery from acute viral hepatitis despite active maintenance of a cytotoxic T-lym-phocyte response. Nat Med. 1996; 2:1104–1108.

4. Liaw YF, Sheen IS, Chen TJ, Chu CM, Pao CC. Incidence, determinants and significance of delayed clearance of serum HBsAg in chronic hepatitis B virus infection: a prospective study. Hepatology. 1991; 13:627–631.

5. Loriot MA, Marcellin P, Walker F, et al. Persistence of hepatitis B virus DNA in serum and liver from patients with chronic hepatitis B after loss of HBsAg. J Hepatol. 1997; 27:251–258.

6. Raimondo G, Allain JP, Brunetto MR, et al. Statements from the Taormina expert meeting on occult hepatitis B virus infection. J Hepatol. 2008; 49:652–657.

7. Mariscal LF, Rodríguez-Iñigo E, Bartolomé J, et al. Hepatitis B infection of the liver in chronic hepatitis C without detectable hepatitis B virus DNA in serum. J Med Virol. 2004; 73:177–186.

8. Torbenson M, Thomas DL. Occult hepatitis B. Lancet Infect Dis. 2002; 2:479–486.

9. Hollinger FB, Sood G. Occult hepatitis B virus infection: a covert operation. J Viral Hepat. 2010; 17:1–15.

10. Raimondo G, Pollicino T, Romanò L, Zanetti AR. A 2010 update on occult hepatitis B infection. Pathol Biol (Paris). 2010; 58:254–257.

11. Schmeltzer P, Sherman KE. Occult hepatitis B: clinical implications and treatment decisions. Dig Dis Sci. 2010; 55:3328–3335.

12. Bréchot C, Thiers V, Kremsdorf D, Nalpas B, Pol S, Paterlini-Bréchot P. Persistent hepatitis B virus infection in subjects without hepatitis B surface antigen: clinically significant or purely "occult"? Hepatology. 2001; 34:194–203.

13. Cacciola I, Pollicino T, Squadrito G, et al. Quantification of intrahepatic hepatitis B virus (HBV) DNA in patients with chronic HBV infection. Hepatology. 2000; 31:507–512.

14. Pollicino T, Raffa G, Costantino L, et al. Molecular and functional analysis of occult hepatitis B virus isolates from patients with hepatocellular carcinoma. Hepatology. 2007; 45:277–285.

15. Nalpas B, Pourcel C, Feldmann G, et al. Chronic alcohol intoxication decreases the serum level of hepatitis B surface antigen in transgenic mice. J Hepatol. 1992; 15:118–124.

16. Lok ASF. Occult hepatitis B virus infection: diagnosis, implications and management? J Gastroenterol Hepatol. 2004; 19(Suppl):114–117.

17. Zerbini A, Pilli M, Boni C, et al. The characteristics of the cellmediated immune response identify different profiles of occult hepatitis B virus infection. Gastroenterology. 2008; 134:1470–1481.

18. Conjeevaram HS, Lok AS. Occult hepatitis B virus infection: a hidden menace? Hepatology. 2001; 34:204–206.

19. Raimondo G, Navarra G, Mondello S, et al. Occult hepatitis B virus in liver tissue of individuals without hepatic disease. J Hepatol. 2008; 48:743–746.

20. Ocana S, Casas ML, Buhigas I, Lledo JL. Diagnostic strategy for occult hepatitis B virus infection. World J Gastroenterol. 2011; 17:1553–1557.

21. Kim YS, Jang JY, Eun SH, et al. Detection of intrahepatic HBV DNA in HBsAg-negative liver diseases. Korean J Hepatol. 2006; 12:201–208.

22. Kim SM, Lee KS, Park CJ, et al. Prevalence of occult HBV infection among subjects with normal serum ALT levels in Korea. J Infect. 2007; 54:185–191.

23. Chemin I, Zoulim F, Merle P, et al. High incidence of hepatitis B infections among chronic hepatitis cases of unknown aetiology. J Hepatol. 2001; 34:447–454.

24. Pollicino T, Squadrito G, Cerenzia G, et al. Hepatitis B virus maintains its pro-oncogenic properties in the case of occult HBV infection. Gastroenterology. 2004; 126:102–110.

25. Chemin I, Trépo C. Clinical impact of occult HBV infections. J Clin Virol. 2005; 34(Suppl 1):S15–S21.

26. Fang Y, Shang QL, Liu JY, et al. Prevalence of occult hepatitis B virus infection among hepatopathy patients and healthy people in China. J Infect. 2009; 58:383–388.

27. Yuen MF, Lee CK, Wong DK, 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; 59:1389–1393.

28. Cacciola I, Pollicino T, Squadrito G, Cerenzia G, Orlando ME, Raimondo G. Occult hepatitis B virus infection in patients with chronic hepatitis C liver disease. N Engl J Med. 1999; 341:22–26.

29. Jang JY, Jeong SW, Cheon SR, et al. Clinical significance of occult hepatitis B virus infection in chronic hepatitis C patients. Korean J Hepatol. 2011; 17:206–212.

30. Sagnelli E, Coppola N, Scolastico C, Mogavero AR, Filippini P, Piccinino F. HCV genotype and "silent" HBV coinfection: two main risk factors for a more severe liver disease. J Med Virol. 2001; 64:350–355.

31. Fukuda R, Ishimura N, Niigaki M, et al. Serologically silent hepatitis B virus coinfection in patients with hepatitis C virus-associated chronic liver disease: clinical and virological significance. J Med Virol. 1999; 58:201–207.

32. Koike K, Kobayashi M, Gondo M, Hayashi I, Osuga T, Takada S. Hepatitis B virus DNA is frequently found in liver biopsy samples from hepatitis C virus-infected chronic hepatitis patients. J Med Virol. 1998; 54:249–255.

33. Chakravarti A, Verma V, Jain M, Kar P. Characteristics of dual infection of hepatitis B and C viruses among patients with chronic liver disease: a study from tertiary care hospital. Trop Gastroenterol. 2005; 26:183–187.

34. Shih CM, Lo SJ, Miyamura T, Chen SY, Lee YH. Suppression of hepatitis B virus expression and replication by hepatitis C virus core protein in HuH-7 cells. J Virol. 1993; 67:5823–5832.

35. 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; 39:51–57.

36. Minuk GY, Sun DF, Greenberg R, et al. Occult hepatitis B virus infection in a North American adult hemodialysis patient population. Hepatology. 2004; 40:1072–1077.

37. Besisik F, Karaca C, Akyüz F, et al. Occult HBV infection and YMDD variants in hemodialysis patients with chronic HCV infection. J Hepatol. 2003; 38:506–510.

38. Raimondo G, Pollicino T, Cacciola I, Squadrito G. Occult hepatitis B virus infection. J Hepatol. 2007; 46:160–170.

39. Iizuka H, Ohmura K, Ishijima A, et al. Correlation between anti-HBc titers and HBV DNA in blood units without detectable HBsAg. Vox Sang. 1992; 63:107–111.