- About this Journal ·
- Abstracting and Indexing ·
- Aims and Scope ·
- Annual Issues ·
- Article Processing Charges ·
- Articles in Press ·
- Author Guidelines ·
- Bibliographic Information ·
- Citations to this Journal ·
- Contact Information ·
- Editorial Board ·
- Editorial Workflow ·
- Free eTOC Alerts ·
- Publication Ethics ·
- Reviewers Acknowledgment ·
- Submit a Manuscript ·
- Subscription Information ·
- Table of Contents
BioMed Research International
Volume 2013 (2013), Article ID 859583, 7 pages
Prevalence of Occult Hepatitis B Virus Infection in a Cohort of HIV-Positive Patients Resident in Sicily, Italy
1Department of Sciences for the Health Promotion and Mother and Child Care “G. D’Alessandro”, Hygiene Section, University of Palermo, 133 Via del Vespro, 90127 Palermo, Italy
2Department of Sciences for the Health Promotion and Mother and Child Care “G. D’Alessandro”, Infectious Diseases Section, University of Palermo, 133 Via del Vespro, 90127 Palermo, Italy
Received 30 April 2013; Revised 12 July 2013; Accepted 25 July 2013
Academic Editor: Esteban Martinez
Copyright © 2013 Fabio Tramuto et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Occult hepatitis B virus (OBI) in HIV-infected groups is still debated, as well as the associated risk-factors and clinical significance. In this paper, we examined a total of 405 HBsAg-negative/HIV-infected patients enrolled from January 2007 to December 2009. Overall, the prevalence of OBI was 5.9% (95% confidence interval (CI95%): 3.8–8.7%); it was more frequently associated with “anti-HBc alone” serological marker (11.3%; adjusted odds ratio = 3.7, CI95%: 1.4–9.8), although it was also detected in the absence of any HBV serological marker (4.9%; CI95%: 2.3–9.1%). A low prevalence of anti-HCV-positive patients with OBI was found (3.1%; CI95%: 0.6–8.7%). HIV RNA plasma levels or other immunological/clinical characteristics were not significantly associated with OBI. All but one occult HBV infections were sustained by genotype D viral strains. OBI is relatively frequent in HIV-infected patients, although it does not seem to exert a relevant clinical impact. Viral genotypes in occult HBV infections reflect those circulating in the Mediterranean area.
The term “occult” hepatitis B infection (OBI) is defined by the presence of HBV DNA in plasma and/or liver tissue of subjects who lack detectable hepatitis B surface antigen (HBsAg).
Occult HBV infections are more frequently detected in individuals with antibodies to hepatitis B core antigen (anti-HBc) , often as unique marker of HBV infection [2, 3]. Nevertheless, recent estimates suggest that up to 20% of individuals with occult HBV could be negative even for anti-HBc antibodies or any other serological indicator of exposure to HBV , indicating that diagnosis of occult HBV infection is still an unresolved issue .
Nevertheless, occult HBV infection has important implications in HIV coinfected groups, being associated with faster rate of liver disease progression toward cirrhosis and hepatocellular carcinoma .
Although the impact of occult HBV infection has been investigated in different countries [3, 7, 9, 12–14] and clinical settings , no data are available on the prevalence of OBI among HIV-positive individuals from our geographic area.
A cross-sectional retrospective study was carried out with the aim of assessing the prevalence, risk factors, and genotypic characteristics of occult HBV infection in a cohort of HIV-infected individuals living in Sicily, either naïve or treated with HAART.
2. Materials and Methods
2.1. Study Population
A cross-sectional retrospective study was carried out on a total of 405 HBsAg-negative/HIV-positive subjects (median age 41.0 years, 67.9% males) admitted to the Infectious Diseases ward of the University Hospital “P. Giaccone,” Palermo, Italy, from January 2007 to December 2009, in day-hospital regimen for clinical followup of HIV infection.
All demographic, clinical, and laboratory data were stored according to the Italian laws on privacy, and the research was conducted following the Helsinki Declaration statements. The study was reviewed and approved by the institutional review board of the university hospital.
2.2. Laboratory Analysis
Plasma samples of HIV-infected patients were collected and kept frozen at −80°C until further analysis. HBV/HCV serological markers of infection were evaluated for routinary examination by the use of third-generation enzyme-linked-immunosorbent assays (Vitros Immunodiagnostics, Ortho-Clinical Diagnostics, High Wycombe, UK), and anti-HCV-positive samples were confirmed with a third-generation recombinant-immunoblot assay (RIBA) (Ortho-Clinical Diagnostics, High Wycombe, UK).
In addition, for the baseline evaluation of liver injury, some biochemical parameters were tested: alanine/aspartate aminotransferase (ALT/AST), total/direct/indirect bilirubin, gamma-glutamyl-transferase, and alkaline phosphatase (Ortho-Clinical Diagnostics, High Wycombe, UK).
Detection of occult HBV infection was carried out in agreement with the key recommendations of EASL consensus conference . In this regard, up to 1 mL of plasma sample collected from HBsAg-negative patients was used during RNA extraction, and three different in-house nested-PCR amplification assays were applied to detect pre-S/S, pre-Core/Core, and Pol HBV viral sequences, respectively . Appropriate negative and positive controls were included in each PCR reaction.
In our study, a “case of occult HBV infection” was defined as a PCR-positivity in at least one of the three HBV domains defined, after a confirmation of its specificity by sequencing .
Viral nucleotide sequences obtained from each PCR-positive sample were submitted to the web-based genotyping program at the National Center for Biotechnology Information (NCBI) (http://www.ncbi.nlm.nih.gov/projects/genotyping/formpage.cgi) to identify the corresponding HBV genotype.
All tests were performed at the Molecular Epidemiology Laboratory of the Department of Sciences for Health Promotion and Mother and Child Care “G. D’Alessandro,” Hygiene section, University of Palermo, Italy.
2.3. Statistical Analysis
Descriptive statistics were calculated and reported for sociodemographic and clinical characteristics. Median and interquartile ranges (IQRs) were used for description of continuous variables, while frequency analyses for categorical variables were described with the use of percentages.
According to data distribution, comparisons of continuous variables were conducted by using Students -test or Mann-Whitney test, while categorical variables were compared with the Chi-square test or Fisher’s exact test, as appropriate. A value < 0.05 was considered to indicate statistical significance.
A logistic regression analysis was used to examine the association between occult HBV status and specific serological pattern of viral infection, and the results were expressed as odds ratios (ORs) with 95% confidence intervals (CIs).
Statistic analysis was performed by using STATA for Apple (version 12.1 MP, StataCorp, College Station, TX, USA).
Table 1 describes the sociodemographic and serological characteristics of the study population. The study group consisted of 405 HBsAg-negative/HIV-positive subjects (275 males and 130 females, M : F ratio = 2.1) with a median age of 41.0 years (IQR = 14.2 years); females were slightly younger than males (40.3 years versus 41.7 years, resp.).
More than two-thirds of subjects (78.5%, ) reported promiscuous sexual activity as risk behaviour associated to HIV positivity, while intravenous drug use (IVDU) was prevalent among HIV/HCV coinfected patients (44.9%, ).
The cohort of subjects presented in this paper mainly consisted of native Italians (82.7%, ), 15.6% () were Africans, and only a minority originated from other geographic regions including Eastern Europe (1.7%, ).
According to the HBV/HCV serological status, five different categories were identified. One hundred eighty-three HIV-positive individuals (45.2%) were negative to all of the serological markers of HBV infection performed in this study, 88 (21.7%) were anti-HBs + anti-HBc positive, 71 (17.5%) showed the serological profile “anti-HBc alone,” and 63 (15.6%) were positive to anti-HBs as unique marker of infection. Overall, 24.2% of HIV-positive subjects () were coinfected with HCV; the anti-HBc alone pattern was more frequently detected in HCV c-infected individuals than in HCV-negative subjects (38.8% versus 10.7%; OR = 5.3, ).
DNA sequences of hepatitis B viruses were detected in 24 out of 405 patients (Table 2(a)), corresponding to a cumulative prevalence of occult HBV of 5.9% (CI95%: 3.8–8.7%).
HBV DNA resulted more frequently associated to the serological pattern anti-HBc alone (11.3%, ), followed by anti-HBs + anti-HBc (6.8%, ), and no HBV markers (4.9%, ). Moreover, HBV DNA sequences were detected in 3 out of 98 patients coinfected with HCV (3.1%), of whom two showed the pattern anti-HBc alone.
HIV RNA plasma levels were lower among HBV DNA-negative than -positive individuals (1.8 log10 HIV RNA copies/mL versus 2.8 log10 HIV RNA copies/mL), although about half of OBI cases (41.7%, ) had undetectable HIV viral load (≤50 HIV RNA copies/mL).
Overall, one hundred forty-five subjects (35.8%) were naïve to HAART. The most part of patients with known HAART regimens (75.1%, ) were taking a therapy including lamivudine, with similar proportions between HBV DNA-negative and -positive subjects (74.5%, versus 84.6%, ). The median time of exposure to antiretrovirals did not differ between OBI and non-OBI patients.
Immune status was also explored comparing the two HBV DNA groups. The cell counts of HIV-infected patients were found to be similar between groups (388 cells/mL versus 419 cells/mL, ), and a higher proportion of subjects with counts ≤ 200 cells/mL was observed in the HBV-DNA negative group in respect to the HBV DNA-positive group (22.9%, versus 20.0%, ), although the difference was not statistically supported.
Plasma concentrations of biochemical indicators of liver damage were substantially similar in the two HBV groups considered, either in the cohort as a whole or in HAART-naïve subjects (data not shown).
Finally, each HIV-positive patient with occult HBV infection was genetically characterized for viral HBV genotype classification. Almost the totality of patients with OBI were collected during the period 2008-2009 and were infected by genotype D viruses; only one subject, native of sub-Saharan Africa, harboured a genotype E hepatitis B virus (Table 2(b)).
In the present study, a cohort of 405 HBsAg-negative/HIV-infected individuals was investigated in order to assess the impact of occult HBV infection in Sicily, and an overall prevalence of 5.9% (CI95%: 3.8–8.7%) was found.
In Italy, the prevalence of OBI has been previously evaluated in different clinical settings [3, 9, 14, 17–19], and, to our knowledge, this is the first work carried out in our geographic area on a cohort of HIV-infected patients.
In this specific high-risk group, several studies have been conducted worldwide and the available data on the frequency of occult HBV infection are widely divergent, ranging from 0% to more than 90% [6–10], mostly depending on differences in terms of sensitivity limit of the assay used (standard/nested PCR, real-time PCR, etc.), number of HBV DNA domains examined, biological compartment explored (liver, plasma, or both), and composition of the study populations [1, 20, 21].
This work confirms that occult HBV can be detected either in patients with serological evidence of past “apparently resolved” HBV infection, but also in individuals with no evident history of exposure to HBV .
The prevalence of OBI presented in this paper is quite similar to that reported in European countries such as The Netherlands , consistently higher than that observed in Spain , France , or Taiwan  (0.7%, 0.6%, and 2.3%, resp.), but lower than that reported in countries either at low or high rates of chronic HBV [7, 20, 24].
In Sicily, the impact of OBI has been recently investigated in different groups of subjects belonging to low- and high-risk HBV exposure, such as general population, intravenous drug users, patients with hepatocellular carcinoma, and immigrants from geographic areas with high rate of HBV infection [3, 14].
In accordance to other authors [9, 22, 25, 26], our findings add consistency to the role of the anti-HBc alone profile as the most adequate serological surrogate of OBI, being the only factor significantly associated to a greater probability of OBI detection, although higher prevalence of anti-HBc alone does not necessarily reflect significantly higher frequency of OBI [3, 9, 14, 22, 25, 26]. HIV infection has been proposed to have a major effect on OBI, leading to more consistent levels in symptomatic HIV as compared to asymptomatic HIV , being significantly associated with lower cell counts .
In our experience, although HBV DNA-positive patients showed higher levels of HIV RNA, the median cell counts were not significantly different when compared to HBV DNA-negative group, and OBI cases were quite similarly represented independently to plasma levels.
Overall, the contribution of occult HBV to liver damage remains unclear. Although ALT/AST flares have been observed in HCV-positive patients in association with occult HBV , in our series we did not find abnormal levels of biochemical indicators of liver injury in OBI-positive patients, in accordance to the overall trend in the literature [9, 18, 29], also in correlation to the immunosuppressed state of HIV-positive subjects [12, 30].
In general, HCV coinfection has been considered as one of the main reasons for inducing OBI , and prevalences of occult HBV infection have been reported to be significantly higher in HCV chronically coinfected patients as compared to HCV-negative individuals [32, 33].
In Italy, the impact of OBI in cohorts of HIV-positive patients coinfected with hepatitis C virus was recently investigated, either in plasma samples or liver biopsies [9, 18], reporting consistent prevalences of OBI and suggesting a strong correlation with HCV. Nevertheless, in accordance with other recently published studies [34, 35], in our cohort occult HBV infection was uncommon among anti-HCV positive subjects, and the high frequency of HAART-treated individuals within this specific group (most of them assuming a lamivudine-based therapy) could partially explain the low prevalence found [36, 37].
The positive association between HIV and chronic hepatitis B infection is well known, in terms of higher levels of HBV DNA and detection of HBV antigens [38, 39], especially before the availability of HAART. More recently, the widespread introduction of HAART in clinical practice, commonly associated with HIV/HBV dually active drugs (i.e. lamivudine, tenofovir, and emtricitabine), plays an important role in the suppression of virus replication , leading to lower levels of OBI in HAART-treated HIV-positive subjects.
However, as similarly reported by other authors in Italy [9, 40], in our study population occult HBV infections were found either in HAART naïve or treated patients, and lamivudine-based HAART did not exert an important effect on HBV DNA detectability.
Finally, in this study, the most part of occult infections were sustained by genotype D HBV viral strains, which is consistent with the genotypes circulating in Sicily . In this regard, although it has been suggested that in occult HBV infection preferentially occurring genotype D viruses [9, 35, 41–43], HBV genotypes other than D, including the C genotype [44, 45] as well as A, G, and E genotypes [14, 22, 46], have been detected in OBI.
Our findings should be interpreted in light of the possible limitations of this study, including the cross-sectional retrospective design, the use of a single time point testing without any followup, and the biological compartment explored to detect HBV-DNA. Moreover, the limited sample size may have reduced our ability to detect differences between groups, and the results, as such, may not be generalizable to other settings.
Nevertheless, despite these limitations, our results add evidence to the knowledge in this field, in a geographic area where the increasing trend in migration flows could play an important role in promoting a modification of the local HBV epidemiology.
The surveillance of occult HBV infection and its genetic variability is recommended to better evaluate the viral dynamics and their role in the outcome of the liver damage in HIV/HCV coinfected as well as in healthy individuals with HBV serological pattern suggestive of latent HBV infection.
Conflict of Interests
All authors report no conflict of interests.
- G. Raimondo, T. Pollicino, I. Cacciola, and G. Squadrito, “Occult hepatitis B virus infection,” Journal of Hepatology, vol. 46, no. 1, pp. 160–170, 2007.
- S. Urbani, F. Fagnoni, G. Missale, and M. Franchini, “The role of anti-core antibody response in the detection of occult hepatitis B virus infection,” Clinical Chemistry and Laboratory Medicine, vol. 48, no. 1, pp. 23–29, 2010.
- F. Vitale, F. Tramuto, A. Orlando et al., “Can the serological status of “anti-HBc alone” be considered a sentinel marker for detection of “occult” HBV infection?” Journal of Medical Virology, vol. 80, no. 4, pp. 577–582, 2008.
- M. Torbenson and D. L. Thomas, “Occult hepatitis B,” The Lancet Infectious Diseases, vol. 2, no. 8, pp. 479–486, 2002.
- S. Levicnik-Stezinar, U. Rahne-Potokar, D. Candotti, N. Lelie, and J. Allain, “Anti-HBs positive occult hepatitis B virus carrier blood infectious in two transfusion recipients,” Journal of Hepatology, vol. 48, no. 6, pp. 1022–1025, 2008.
- J. W. T. Stuart, M. Velema, R. Schuurman, C. A. B. Boucher, and A. I. M. Hoepelman, “Occult hepatitis B in persons infected with HIV is associated with low CD4 counts and resolves during antiretroviral therapy,” Journal of Medical Virology, vol. 81, no. 3, pp. 441–445, 2009.
- S. Gupta and S. Singh, “Occult hepatitis B virus infection in ART-naive HIV-infected patients seen at a tertiary care centre in north India,” BMC Infectious Diseases, vol. 10, article 53, 2010.
- M. Hofer, H. I. Joller-Jemelka, P. J. Grob, R. Lüthy, and M. Opravil, “Frequent chronic hepatitis B virus infection in HIV-infected patients positive for antibody to hepatitis B core antigen only,” European Journal of Clinical Microbiology and Infectious Diseases, vol. 17, no. 1, pp. 6–13, 1998.
- G. Morsica, F. Ancarani, S. Bagaglio et al., “Occult hepatitis B virus infection in a Cohort of HIV-positive patients: correlation with hepatitis C virus coinfection, virological and immunological features,” Infection, vol. 37, no. 5, pp. 445–449, 2009.
- M. Rodríguez-Torres, J. Gonzalez-Garcia, N. Braü et al., “Occult hepatitis B virus infection in the setting of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection: clinically relevant or a diagnostic problem?” Journal of Medical Virology, vol. 79, no. 6, pp. 694–700, 2007.
- D. Kremsdorf, P. Soussan, P. Paterlini-Brechot, and C. Brechot, “Hepatitis B virus-related hepatocellular carcinoma: paradigms for viral-related human carcinogenesis,” Oncogene, vol. 25, no. 27, pp. 3823–3833, 2006.
- T. G. Bell, E. Makondo, N. A. Martinson, and A. Kramvis, “Hepatitis B virus infection in human immunodeficiency virus infected southern African adults: occult or overt—that is the question,” PLoS ONE, vol. 7, no. 10, Article ID e45750, 8 pages, 2012.
- F. A. Di Lello, J. Macías, C. C. Cifuentes, J. Vargas, J. C. Palomares, and J. A. Pineda, “Low prevalence of occult HBV infection among HIV-infected patients in southern Spain,” Enfermedades Infecciosas y Microbiologia Clinica, vol. 30, no. 6, pp. 312–314, 2012.
- F. Tramuto, C. M. Maida, G. M. Colomba et al., “Occult hepatitis B infection in the immigrant population of sicily, Italy,” Journal of Immigrant and Minority Health, vol. 15, no. 4, pp. 725–731, 2012.
- S. M. Alavian, S. M. Miri, F. B. Hollinger, and S. M. Jazayeri, “Occult hepatitis B, (OBH) in clinical settings,” Hepatitis Monthly, vol. 12, no. 8, Article ID e6126, 8 pages, 2012.
- G. Raimondo, J. Allain, M. R. Brunetto et al., “Statements from the Taormina expert meeting on occult hepatitis B virus infection,” Journal of Hepatology, vol. 49, no. 4, pp. 652–657, 2008.
- A. Costantini, K. Marinelli, G. Biagioni et al., “Molecular analysis of hepatitis B virus (HBV) in an HIV co-infected patient with reactivation of occult HBV infection following discontinuation of lamivudine-including antiretroviral therapy,” BMC Infectious Diseases, vol. 11, article 310, 2011.
- P. Fabris, M. R. Biasin, M. T. Giordani et al., “Impact of occult HBV infection in HIV/HCV co-infected patients: HBV-DNA detection in liver speciments and in serum samples,” Current HIV Research, vol. 6, no. 2, pp. 173–179, 2008.
- D. Ferraro, P. Pizzillo, N. Urone, E. Iannitto, A. Craxi, and R. Di Stefano, “Viral sequence analysis of occult HBV infection and its reactivation in immunosuppressed patients,” Journal of Biological Regulators & Homeostatic Agents, vol. 26, no. 3, pp. 457–465, 2012.
- K. Azadmanesh, M. Mohraz, A. Aghakhani et al., “Occult hepatitis B virus infection in HIV-infected patients with isolated hepatitis B core antibody,” Intervirology, vol. 51, no. 4, pp. 270–274, 2008.
- D. Neau, M. Winnock, A. Jouvencel et al., “Occult hepatitis B virus infection in HIV-infected patients with isolated antibodies to hepatitis B core antigen: aquitaine cohort, 2002-2003,” Clinical Infectious Diseases, vol. 40, no. 5, pp. 750–753, 2005.
- C. Firnhaber, C. Y. Chen, D. Evans et al., “Prevalence of hepatitis B virus (HBV) co-infection in HBV serologically-negative South African HIV patients and retrospective evaluation of the clinical course of mono- and co-infection,” International Journal of Infectious Diseases, vol. 16, no. 4, pp. e268–e272, 2012.
- S. Liang, T. Chen, S. S. Lee et al., “Risk factors of isolated antibody against core antigen of hepatitis B virus: association with HIV infection and age but not hepatitis C virus infection,” Journal of Acquired Immune Deficiency Syndromes, vol. 54, no. 2, pp. 122–128, 2010.
- A. Ramezani, M. Mohraz, A. Aghakhani et al., “Frequency of isolated hepatitis B core antibody in HIV-hepatitis C virus co-infected individuals,” International Journal of STD and AIDS, vol. 20, no. 5, pp. 336–338, 2009.
- R. T. Gandhi, A. Wurcel, H. Lee et al., “Isolated antibody to hepatitis B core antigen in human immunodeficiency virus type-1-infected individuals,” Clinical Infectious Diseases, vol. 36, no. 12, pp. 1602–1605, 2003.
- M. J. Mphahlele, A. Lukhwareni, R. J. Burnett, L. M. Moropeng, and J. M. Ngobeni, “High risk of occult hepatitis B virus infection in HIV-positive patients from South Africa,” Journal of Clinical Virology, vol. 35, no. 1, pp. 14–20, 2006.
- L. I. Compston, C. Li, F. Sarkodie, S. Owusu-Ofori, O. Opare-Sem, and J. Allain, “Prevalence of persistent and latent viruses in untreated patients infected with HIV-1 from Ghana, West Africa,” Journal of Medical Virology, vol. 81, no. 11, pp. 1860–1868, 2009.
- R. Kannangai, P. Vivekanandan, D. Netski et al., “Liver enzyme flares and occult hepatitis B in persons with chronic hepatitis C infection,” Journal of Clinical Virology, vol. 39, no. 2, pp. 101–105, 2007.
- N. M. Araujo, M. Branco-Vieira, A. C. M. Silva et al., “Occult hepatitis B virus infection in HIV-infected patients: evaluation of biochemical, virological and molecular parameters,” Hepatology Research, vol. 38, no. 12, pp. 1194–1203, 2008.
- W. H. Gerlich, C. Bremer, M. Saniewski et al., “Occult hepatitis B virus infection: detection and significance,” Digestive Diseases, vol. 28, no. 1, pp. 116–125, 2010.
- V. Carreño, J. Bartolomé, I. Castillo, and J. A. Quiroga, “Occult hepatitis B virus and hepatitis C virus infections,” Reviews in Medical Virology, vol. 18, no. 3, pp. 139–157, 2008.
- C. Cardoso, A. L. Alves, F. Augusto et al., “Occult hepatitis B infection in Portuguese patients with chronic hepatitis C liver disease: prevalence and clinical significance,” European Journal of Gastroenterology & Hepatology, vol. 25, no. 2, pp. 142–146, 2013.
- I. Elgohry, A. Elbanna, and D. Hashad, “Occult hepatitis B virus infection in a cohort of Egyptian chronic hemodialysis patients,” Clinical Laboratory, vol. 58, no. 9-10, pp. 1057–1061, 2012.
- M. A. Abu El Makarem, M. Abdel Hamid, A. Abdel Aleem et al., “Prevalence of occult hepatitis B virus infection in hemodialysis patients from egypt with or without hepatitis C virus infection,” Hepatitis Monthly, vol. 12, no. 4, pp. 253–258, 2012.
- M. K. Arababadi, A. A. Pourfathollah, A. Jafarzadeh et al., “Hepatitis B virus genotype, HBsAg mutations and co-infection with HCV in occult HBV infection,” Clinics and Research in Hepatology and Gastroenterology, vol. 35, no. 8-9, pp. 554–559, 2011.
- N. Coppola, G. Tonziello, M. Pisaturo et al., “Reactivation of overt and occult hepatitis B infection in various immunosuppressive settings,” Journal of Medical Virology, vol. 83, no. 11, pp. 1909–1916, 2011.
- P. Filippini, N. Coppola, R. Pisapia et al., “Impact of occult hepatitis B virus infection in HIV patients naive for antiretroviral therapy,” AIDS, vol. 20, no. 9, pp. 1253–1260, 2006.
- N. J. Bodsworth, D. A. Cooper, and B. Donovan, “The influence of human immunodeficiency virus type 1 infection on the development of the hepatitis B virus carrier state,” Journal of Infectious Diseases, vol. 163, no. 5, pp. 1138–1140, 1991.
- S. C. Hadler, F. N. Judson, P. M. O'Malley et al., “Outcome of hepatitis B virus infection in homosexual men and its relation to prior human immunodeficiency virus infection,” Journal of Infectious Diseases, vol. 163, no. 3, pp. 454–459, 1991.
- S. Bagaglio, L. Porrino, A. Lazzarin, and G. Morsica, “Molecular characterization of occult and overt hepatitis B (HBV) infection in an HIV-infected person with reactivation of HBV after antiretroviral treatment interruption,” Infection, vol. 38, no. 5, pp. 417–421, 2010.
- B. Pinarbasi, D. Onel, F. Cosan et al., “Prevalence and virological features of occult hepatitis B virus infection in female sex workers who work uncontrolled in Turkey,” Liver International, vol. 29, no. 2, pp. 227–230, 2009.
- S. Ramia, A. I. Sharara, M. El-Zaatari, F. Ramlawi, and Z. Mahfoud, “Occult hepatitis B virus infection in Lebanese patients with chronic hepatitis C liver disease,” European Journal of Clinical Microbiology and Infectious Diseases, vol. 27, no. 3, pp. 217–221, 2008.
- K. M. Weinberger, T. Bauer, S. Böhm, and W. Jilg, “High genetic variability of the group-specific a-determinant of hepatitis B virus surface antigen (HBsAg) and the corresponding fragment of the viral polymerase in chronic virus carriers lacking detectable HBsAg in serum,” Journal of General Virology, vol. 81, part 5, pp. 1165–1174, 2000.
- Y. Fang, X. Teng, W. Xu et al., “Molecular characterization and functional analysis of occult hepatitis B virus infection in Chinese patients infected with genotype C,” Journal of Medical Virology, vol. 81, no. 5, pp. 826–835, 2009.
- Z. Fang, H. Zhuang, X. Wang, X. Ge, and T. J. Harrison, “Hepatitis B virus genotypes, phylogeny and occult infection in a region with a high incidence of hepatocellular carcinoma in China,” World Journal of Gastroenterology, vol. 10, no. 22, pp. 3264–3268, 2004.
- M. R. Pourkarim, P. Lemey, S. Amini-Bavil-Olyaee et al., “Molecular characterization of hepatitis B virus strains circulating in Belgian patients co-infected with HIV and HBV: overt and occult infection,” Journal of Medical Virology, vol. 83, no. 11, pp. 1876–1884, 2011.