I read with great interest the paper by Taheri et al. published in HEPATITIS Monthly (Number 31, February 2011). The results of this follow-up study are hopeful of HEPATITIS-B vaccine efficacy in patients who lost HBsAg and did not seroconvert to anti-HBs with no detectable HBV DNA. However, the editorial in the same issue, as well as Taheri et al. themselves, noted some important limitations to this study.

OCCULT HEPATITIS B (OHB) is not a new entity and there are many reports of patients with HEPATITIS B virus (HBV) evidence replication in the absence of detectable HEPATITIS B surface antigen (HBsAg) and occasionally other HBV serologic markers. After introducing highly sensitive and specific tests for HBs Ag and HBV DNA, the diagnosis of OBH is easier and the importance of clinical entity of OBH is more controversial. In this issue of HEPATITIS Monthly, Abu El Makarem reported the prevalence of OCCULT HEPATITIS B virus infection in hemodialysis patients from Egypt with considering the HEPATITIS C Virus (HCV) Infection.

Background: OCCULT HEPATITIS B infection (OBI) is determined by finding HEPATITIS B virus (HBV)DNAin the liver cells of the patients with negative tests for HBV surface antigen. It is more common in patients with HEPATITIS C virus (HCV) infection which can be transmitted by blood transfusion and is frequently seen in hemophilia and thalassemia patients. Objectives: The aim of this study was to assess the prevalence of OBI among Iranian patients with hematological disorders (thalassemia, hemophilia and other coagulation factor deficiencies) infected with chronic HEPATITIS C (CHC). Methods: In this descriptive cross-sectional study, all patients with hematological disorders (thalassemia, hemophilia or other coagulation factor deficiencies) who had simultaneous CHC infection and were referred to the Tehran HEPATITIS center between 2009 and 2010 were enrolled. OCCULT HEPATITIS B infection identification was based on serum HBV-DNA tests. Data analysis was performed with SPSS software. Results: All patients were HBsAg-negative and HCV RNA-positive. Only 145 patients were evaluated for HBV DNA (126 male and 19 female patients). The mean age (SD) was 28. 12 (8. 6) years. Thirty-five patients had thalassemia, 95 patients had hemophilia, and 15 patients had coagulation factor deficiencies. Serum HBV-DNA was negative for all cases. Conclusions: Based on our results, it seems that there were no cases of OBI among chronic HCV-infected patients with thalassemia and bleeding disorders, particularly hemophilia. However, to improve decisions concerning OBI screening, especially in transfusion centers, and concerning the use of comprehensive screening methods, more original studies with more precise laboratory techniques and larger sample sizes are needed.

Diagnosis of HEPATITIS B is routinely based on of serological assay of HEPATITIS B surface antigen (HBsAg). OCCULT HEPATITIS B virus (HBV) infection is generally defined as the detection of HBV-DNA in the serum or tissues of subjects who have negative test for HBsAg. Transmission of HBV infection has been documented from HBsAg negative, anti-HBc positive blood and organ donors. The aim of this study was to determine the rate of OCCULT HBV infection among HBsAg negative and anti- HBc positive blood donors of Rafsanjan blood transfusion center. Sera from 270 healthy blood donors who were negative for both HBsAg and anti-HCV, were tested for anti-HBc antibodies by use of ELISA technique. The samples that were negative for HBsAg but positive for anti-HBc markers also examined for the presence of HBV-DNA by polymerase chain reaction (PCR). Out of 270 HBsAg negative blood samples, 14 samples (5.18%) were positive for anti-HBc antibodies. HBV-DNA was detected in 4/14 (28.57%) of HBsAg negative and anti-HBc positive samples. Moreover, anti-HBs antibody was detected in 2/4 (50%) of HBV-DNA positive samples. These results indicated that HBVDNA found in the majority of HBsAg negative and anti-HBc-positive donors. In addition, the present study recommend the incorporation of routine anti-HBc screening of blood as a surrogate marker of OCCULT HBV infection to prevent some transfusion-transmitted HBV infections.

Context: OCCULT HEPATITIS B virus (HBV) status (OHBS) is simply defined as the presence of HBV DNA in the liver (with or without detectable HBV DNA in the serum), in the absence of serum HBV surface antigen (HBsAg). Importance of OHBS is mostly clinical, related to its possible role in spreading through blood transfusion and liver transplantation; causing classic forms of HBV. Mechanisms underlying this entity are poorly defined. Several possibilities have been suggested, with major classification into two groups: defective host immune response and viral replication activity through mutations of HBV DNA sequence. Mutations are extensively investigated in all four overlapping open reading frames (ORFs) of HBV genome, to define their possible role in the pathogenesis of OHBS. Some of these mutations like S-escape mutants could not be detected by the routine available assays, making them difficult to diagnosis. Therefore, trying to detect this covert condition could be more helpful for defining better preventive and therapeutic strategies.Evidence Acquisition: In the present study we provided an in-depth review of the most important new data available on different mutations in HBV genome of patients with OHBS, which may play a role in the pathogenesis of OHBS. The data were collected through reviewing the full-text articles, identified by the PubMed search, using the following keywords and their different combinations: OCCULT HEPATITIS B, HBV genome, “a” determinant, HBV open reading frames, S mutations, X mutations, P mutations and C mutations.Results: Variants within the major hydrophilic region (MHR) of the HBsAg, deletions in the pre-S1region, codon stop in the S open reading frames (ORF), sporadic non common mutations, some mutations affecting the posttranslational production of HBV proteins in the S ORF like deletion mutations, mutations in start codon and nucleotide changes in the X ORF, deletion and point mutations in P ORF and sometimes, nucleotide substitution in the C ORF are among the assumed mutations detected to have a role in OHBS appearance.Conclusions: Studies mostly lacked a control group and the whole-length HBV sequencing was scant with conflicting results, suggesting that OHBS is often a result of multiple mechanisms. Additional studies on full-length HBV genomes from OCCULT and non-OCCULT HBV cases may shed more light on the interplay between different mechanisms involved in the pathogenesis of OHBS.