Occult hepatitis B infection
Authors: Teresa Pollicino, Giovanni Raimondo
Journal: Journal of Hepatology (2014)

Occult hepatitis B virus (HBV) infection (OBI) is recognized as one of the possible phases in the natural history of chronic HBV infection [[1]EASL Clinical Practice Guidelines Management of chronic hepatitis B virus infection.J Hepatol. 2012; 57: 167-185Abstract Full Text Full Text PDF PubMed Scopus (2697) Google Scholar]. OBI defines the persistence of HBV genomes in the hepatocytes of individuals testing negative for HBV surface antigen (HBsAg) and, usually, also for serum HBV DNA [[2]Raimondo G. Allain J.P. Brunetto M.R. Buendia M.A. Chen D.S. Colombo M. et al.Statements from the Taormina expert meeting on occult hepatitis B virus infection.J Hepatol. 2008; 49: 652-657Abstract Full Text Full Text PDF PubMed Scopus (663) Google Scholar]. Apart from some cases in which the lack of HBsAg detection is attributable to the HBV genetic heterogeneity (i.e., infection with replication-defective variants or with S-escape mutants producing a modified HBsAg undetectable by diagnostic kits), in most cases OBI is related to replication-competent viruses that are strongly suppressed in their activities (replicative and transcriptional) by the host's defense mechanisms. Very importantly, this suppression (a) does not have an absolute effect and residual, low-levels of replication and transcription may persist over time, and (b) may be reversible in particular circumstances leading to viral reactivation and development of a typical HBsAg-positive (namely, "overt") infection [3Raimondo G. Caccamo G. Filomia R. Pollicino T. Occult HBV infection.Semin Immunopathol. 2013; 35: 39-52Crossref PubMed Scopus (170) Google Scholar, 4Zoulim F. New insight on hepatitis B virus persistence from the study of intrahepatic viral cccDNA.J Hepatol. 2005; 42: 302-308Abstract Full Text Full Text PDF PubMed Scopus (219) Google Scholar, 5Michalak T.I. Mulrooney P.M. Coffin C.S. Low doses of hepadnavirus induce infection of the lymphatic system that does not engage the liver.J Virol. 2004; 78: 1730-1738Crossref PubMed Scopus (87) Google Scholar, 6Levrero M. Pollicino T. Petersen J. Belloni L. Raimondo G. Dandri M. Control of cccDNA function in hepatitis B virus infection.J Hepatol. 2009; 51: 581-592Abstract Full Text Full Text PDF PubMed Scopus (442) Google Scholar, 7Zerbini A. Pilli M. Boni C. Fisicaro P. Penna A. Di V.P. et al.The characteristics of the cell-mediated immune response identify different profiles of occult hepatitis B virus infection.Gastroenterology. 2008; 134: 1470-1481Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar, 8Bes M. Vargas V. Piron M. Casamitjana N. Esteban J.I. Vilanova N. et al.T cell responses and viral variability in blood donation candidates with occult hepatitis B infection.J Hepatol. 2012; 56: 765-774Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar, 9Guidotti L.G. Chisari F.V. Noncytolytic control of viral infections by the innate and adaptive immune response.Annu Rev Immunol. 2001; 19: 65-91Crossref PubMed Scopus (861) Google Scholar, 10Pollicino T. Raffa G. Costantino L. Lisa A. Campello C. Squadrito G. et al.Molecular and functional analysis of occult hepatitis B virus isolates from patients with hepatocellular carcinoma.Hepatology. 2007; 45: 277-285Crossref PubMed Scopus (145) Google Scholar, 11Chemin I. Guillaud O. Queyron P.C. 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: 824-825Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar, 12Covolo L. Pollicino T. Raimondo G. Donato F. Occult hepatitis B virus and risk for chronic liver disease: a meta-analysis.Dig Liv Dis. 2013; 45: 238-244Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar, 13Squadrito G. Cacciola I. Alibrandi A. Pollicino T. Raimondo G. Impact of occult hepatitis B virus infection on the outcome of chronic hepatitis C.J Hepatol. 2013; 59: 696-700Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar, 14Shi Y. Wu Y.H. Wu W. Zhang W.J. Yang J. Chen Z. Association between occult hepatitis B virus infection and the risk of hepatocellular carcinoma: a meta-analysis.Liver Int. 2012; 32: 231-240Crossref PubMed Scopus (114) Google Scholar]. The authors declare that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. The authors are grateful to Prof. Carlo Ferrari for his helpful comments and suggestions.