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Fu J, Biao R, Liu Y, Chen J, Zhao H. 24-month outcomes after switching to Dolutegravir/Lamivudine in people living with HIV and HBcAb positivity at the Beijing Ditan Hospital in China. Ann Med 2025; 57:2470957. [PMID: 39992020 PMCID: PMC11852214 DOI: 10.1080/07853890.2025.2470957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Revised: 02/06/2025] [Accepted: 02/07/2025] [Indexed: 02/25/2025] Open
Abstract
BACKGROUND Dolutegravir/lamivudine (DTG/3TC) is a recommended therapy regimen for hepatitis B surface antigen (HBsAg)-negative people living with HIV (PLWH) who have achieved HIV virological suppression or are treatment-naïve. However, this may overlook the impact of occult hepatitis B infection on HIV suppression, which mainly present as hepatitis B core antibody (HBcAb) positive but HBsAg negative. We aim to assess the effect of HBcAb positivity on HIV suppression among PLWH who had switched to DTG/3TC. METHODS A retrospective study was conducted including 127 HBcAb-positive and 474 HBcAb-negative PLWH (all were HBsAg negative) who had switched to DTG/3TC at the Beijing Ditan Hospital in China. HIV-RNA suppression was compared pre-switch (not baseline), at switch, and at 12&24 months post-switch, across three categories: (1) target not detected (TND); (2) HIV RNA < 40 cp/mL; (3) blip. Virological suppression included TND and HIV RNA < 40 cp/mL. Epidemiological (gender, age) and clinical data (CD4 count, HIV viral load, etc.) were extracted from the hospital information system. A p-value < 0.05 was considered statistically significant. RESULT HBcAb-positive PLWH were older at DTG/3TC switch (median age: 41 vs. 36 years old, p < 0.001) and had lower nadir CD4 counts (median nadir CD4 counts: 255 vs. 295, p = 0.011). No difference in TND and HIV RNA < 40 cp/mL was present in the two groups at the switch (HBcAb-positive and -negative: 86.6% vs. 88.8%, 12.6% vs. 10.5%, p = 0.789). Similar HBcAb-positive compared with -negative PLWH resulted in TND at 12&24 months post-switch: 91.4% vs. 91% (p = 0.522) and 88.4% vs. 92.7% (p = 0.249), respectively. Consistent result was observed in HIV RNA < 40 cp/mL. CONCLUSION In the 24-month follow-up after switching to DTG/3TC, HBcAb positivity was not significantly associated with HIV virological suppression.
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Affiliation(s)
- Jiantao Fu
- Clinical Center for HIV/AIDS, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ruojia Biao
- Clinical Center for HIV/AIDS, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Peking University Ditan Teaching Hospital, Beijing, China
| | - Ying Liu
- Clinical Center for HIV/AIDS, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Jing Chen
- Beijing Center for Disease Prevention and Control, Beijing, China
| | - Hongxin Zhao
- Clinical Center for HIV/AIDS, Beijing Ditan Hospital, Capital Medical University, Beijing, China
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2
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Mohareb AM, Menan Kouamé G, Gabassi A, Gabillard D, Moh R, Badje A, Emième A, Maylin S, Ménan H, Hyle EP, Delaugerre C, Danel C, Anglaret X, Lacombe K, Eholié SP, Boyd A. Mortality in relation to hepatitis B virus (HBV) infection status among HIV-HBV co-infected patients in sub-Saharan Africa after immediate initiation of antiretroviral therapy. J Viral Hepat 2021; 28:621-629. [PMID: 33382189 PMCID: PMC7946742 DOI: 10.1111/jvh.13461] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 12/07/2020] [Indexed: 12/12/2022]
Abstract
It is unknown how past and active hepatitis B virus (HBV) infection affect immunorecovery and mortality in people with HIV who initiate tenofovir-based antiretroviral therapy (ART). Using data collected between 2008 and 2015, we studied people with HIV in sub-Saharan Africa initiating immediate ART in the Temprano randomized control trial. We classified participants into HBV groups at ART initiation: hepatitis B surface antigen (HBsAg)-positive with HBV DNA ≥ 2,000 IU/ml; HBsAg-positive with HBV DNA < 2,000 IU/ml; isolated HBcAb-positive; resolved infection (HBsAb-positive/HBcAb-positive); and HBV non-immune/vaccinated (HBcAb-negative). We compared square-root CD4-cell count increases using mixed-effect, non-linear regression adjusted for age, sex, baseline CD4 cell count, and HIV RNA. We compared all-cause mortality using Bayesian parametric survival regression. Among 879 participants, 24 (2.7%) had HBsAg with high HBV DNA, 76 (8.6%) HBsAg with low HBV DNA, 325 (37.0%) isolated anti-HBcAb, 226 (25.7%) resolved HBV infection and 228 (25.9%) HBV non-immune/vaccinated. We found no significant difference in CD4 cell increases between HBV-infection groups after adjustment (p = 0.16). Participants with HBsAg and high HBV DNA had the highest incidence of all-cause mortality (1.9/100 person-years, 95% Credibile Interval [CrI] = 1.0-3.4). By comparison, incidence rates of mortality were reduced by 57% (95%CrI = -79%, -13%), 60% (95%CrI = -82%, -12%) and 66% (95%CrI = -84%, -23%) in those who had isolated anti-HBcAb-positive, resolved HBV infection and HBV non-immune/vaccinated, respectively. In conclusion, individuals with HIV and past HBV infection or isolated anti-HBcAb-positive serology, much like HBV non-immune/vaccinated, experience lower mortality than those with HBsAg and high HBV DNA. Additional HBV-related management would not be necessary for these individuals.
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Affiliation(s)
- Amir M. Mohareb
- Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, USA.,Division of Infectious Diseases, Massachusetts General Hospital, Boston, USA.,Harvard Medical School, Boston, USA
| | - Gérard Menan Kouamé
- Programme PAC-CI site ANRS de Côte d’Ivoire, Abidjan, Côte d’Ivoire.,INSERM UMR1219 IDLIC, Bordeaux, France
| | | | | | - Raoul Moh
- Programme PAC-CI site ANRS de Côte d’Ivoire, Abidjan, Côte d’Ivoire.,Service des Maladies Infectieuses et Tropicale, CHU de Treichville, Abidjan, Côte d’Ivoire
| | - Anani Badje
- Programme PAC-CI site ANRS de Côte d’Ivoire, Abidjan, Côte d’Ivoire.,Service des Maladies Infectieuses et Tropicale, CHU de Treichville, Abidjan, Côte d’Ivoire
| | - Arlette Emième
- Service des Maladies Infectieuses et Tropicale, CHU de Treichville, Abidjan, Côte d’Ivoire
| | - Sarah Maylin
- Laboratoire de Virologie, Hôpital Saint-Louis, AP-HP, Paris, France
| | - Hervé Ménan
- Laboratoire CeDreS, CHU Treichville, Abidjan, Côte d’Ivoire
| | - Emily P. Hyle
- Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, USA.,Division of Infectious Diseases, Massachusetts General Hospital, Boston, USA.,Harvard Medical School, Boston, USA.,Harvard Center for AIDS Research, Boston, USA
| | - Constance Delaugerre
- Laboratoire de Virologie, Hôpital Saint-Louis, AP-HP, Paris, France.,INSERM U944, Institut de Recherche Saint-Louis, Paris, France
| | - Christine Danel
- Programme PAC-CI site ANRS de Côte d’Ivoire, Abidjan, Côte d’Ivoire.,INSERM UMR1219 IDLIC, Bordeaux, France.,University of Bordeaux, France
| | - Xavier Anglaret
- Programme PAC-CI site ANRS de Côte d’Ivoire, Abidjan, Côte d’Ivoire.,INSERM UMR1219 IDLIC, Bordeaux, France.,University of Bordeaux, France
| | - Karine Lacombe
- INSERM, UMR_S1136, Institut Pierre Louis d’Epidémiologie et de Santé Publique, Paris, France.,Service des maladies infectieuses et tropicales, Hôpital Saint-Antoine, AP-HP, Paris, France
| | - Serge P. Eholié
- Programme PAC-CI site ANRS de Côte d’Ivoire, Abidjan, Côte d’Ivoire.,Service des Maladies Infectieuses et Tropicale, CHU de Treichville, Abidjan, Côte d’Ivoire
| | - Anders Boyd
- INSERM, UMR_S1136, Institut Pierre Louis d’Epidémiologie et de Santé Publique, Paris, France.,Corresponding author: Anders Boyd, MPH, PhD, Stichting HIV Monitoring, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands,
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3
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Malagnino V, Teti E, Compagno M, Coppola L, Salpini R, Svicher V, Basso M, Battagin G, Panese S, Rossi MC, Scaggiante R, Zago D, Iannetta M, Parisi SG, Andreoni M, Sarmati L. HBcAb Positivity Is a Risk Factor for an Increased Detectability of HIV RNA after Switching to a Two-Drug Regimen Lamivudine-Based (2DR-3TC-Based) Treatment: Analysis of a Multicenter Italian Cohort. Microorganisms 2021; 9:microorganisms9020396. [PMID: 33671934 PMCID: PMC7919011 DOI: 10.3390/microorganisms9020396] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 02/09/2021] [Accepted: 02/11/2021] [Indexed: 01/31/2023] Open
Abstract
The aim of this study was to evaluate whether the presence of anti-hepatitis B (HBV) c antibodies (HBcAb positivity) could influence the control of Human Immunodeficiency Virus (HIV) viremia in patients living with HIV (PLWH) who switch a to two-drug antiretroviral therapy (2DR) containing lamivudine (3TC) (2DR-3TC). A retrospective observational multicenter study was conducted on 166 PLWH switching to the 2DR-3TC-based regimen: 58 HBcAb-positive and 108 HBcAb-negative patients. The HBcAb-positive PLWH group demonstrated a significantly higher percentage of subjects with very low-level viremia at all time points after switching (6th month: <31% vs. 17.6%, p = 0.047; 12th month 34% vs. 27.5%, p = 0.001; 24th month 37% vs. 34.2, p = 0.003 of the HBcAb-positive and HBcAb-negative groups, respectively) and a higher percentage of subjects with detectable HIV RNA greater than 20 copies/mL 12 and 24 months after switching (12 months 32% vs. 11%, p = 0.001; 24 months 37% vs. 13.9%, p = 0.003 of the HBcAb-positive and HBcAb-negative groups, respectively). Logistic regression analysis showed that an increase in age of ten years (OR 2.48 (95% CI 1.58–3.89), p < 0.0001) and the presence of HBcAb positivity (OR 2.7 (5% CI 1.05–6.9), p = 0.038) increased the risk of detectability of HIV RNA by nearly three-fold after switching to 2DR-3TC.
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Affiliation(s)
- Vincenzo Malagnino
- Clinica di Malattie Infettive, Policlinico Tor Vergata di Roma, 00133 Rome, Italy; (E.T.); (M.C.); (L.C.); (M.I.); (M.A.); (L.S.)
- Dipartimento di Medicina dei Sistemi, Facoltà di Medicina, Università degli studi di Roma Tor Vergata, 00133 Rome, Italy
- Correspondence: ; Tel.: +390-620-902-790
| | - Elisabetta Teti
- Clinica di Malattie Infettive, Policlinico Tor Vergata di Roma, 00133 Rome, Italy; (E.T.); (M.C.); (L.C.); (M.I.); (M.A.); (L.S.)
| | - Mirko Compagno
- Clinica di Malattie Infettive, Policlinico Tor Vergata di Roma, 00133 Rome, Italy; (E.T.); (M.C.); (L.C.); (M.I.); (M.A.); (L.S.)
| | - Luigi Coppola
- Clinica di Malattie Infettive, Policlinico Tor Vergata di Roma, 00133 Rome, Italy; (E.T.); (M.C.); (L.C.); (M.I.); (M.A.); (L.S.)
| | - Romina Salpini
- Dipartimento di Medicina Sperimentale, Università degli Studi di Roma Tor Vergata, 00133 Rome, Italy; (R.S.); (V.S.)
| | - Valentina Svicher
- Dipartimento di Medicina Sperimentale, Università degli Studi di Roma Tor Vergata, 00133 Rome, Italy; (R.S.); (V.S.)
| | - Monica Basso
- Dipartimento di Medicina Molecolare, Università degli Studi di Padova, 35128 Padova, Italy; (M.B.); (D.Z.); (S.G.P.)
| | | | - Sandro Panese
- UOC Malattie Infettive Ospedale di Venezia, 30122 Venezia, Italy;
| | | | - Renzo Scaggiante
- UOC Malattei Infettive, Ospedale di Belluno, 32100 Belluno, Italy;
| | - Daniela Zago
- Dipartimento di Medicina Molecolare, Università degli Studi di Padova, 35128 Padova, Italy; (M.B.); (D.Z.); (S.G.P.)
| | - Marco Iannetta
- Clinica di Malattie Infettive, Policlinico Tor Vergata di Roma, 00133 Rome, Italy; (E.T.); (M.C.); (L.C.); (M.I.); (M.A.); (L.S.)
- Dipartimento di Medicina dei Sistemi, Facoltà di Medicina, Università degli studi di Roma Tor Vergata, 00133 Rome, Italy
| | - Saverio Giuseppe Parisi
- Dipartimento di Medicina Molecolare, Università degli Studi di Padova, 35128 Padova, Italy; (M.B.); (D.Z.); (S.G.P.)
| | - Massimo Andreoni
- Clinica di Malattie Infettive, Policlinico Tor Vergata di Roma, 00133 Rome, Italy; (E.T.); (M.C.); (L.C.); (M.I.); (M.A.); (L.S.)
- Dipartimento di Medicina dei Sistemi, Facoltà di Medicina, Università degli studi di Roma Tor Vergata, 00133 Rome, Italy
| | - Loredana Sarmati
- Clinica di Malattie Infettive, Policlinico Tor Vergata di Roma, 00133 Rome, Italy; (E.T.); (M.C.); (L.C.); (M.I.); (M.A.); (L.S.)
- Dipartimento di Medicina dei Sistemi, Facoltà di Medicina, Università degli studi di Roma Tor Vergata, 00133 Rome, Italy
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4
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Ayana DA, Mulu A, Mihret A, Seyoum B, Aseffa A, Howe R. Occult Hepatitis B virus infection among HIV negative and positive isolated anti-HBc individuals in eastern Ethiopia. Sci Rep 2020; 10:22182. [PMID: 33335238 PMCID: PMC7747707 DOI: 10.1038/s41598-020-79392-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Accepted: 12/02/2020] [Indexed: 01/05/2023] Open
Abstract
The absence of hepatitis B surface antigen (HBsAg) and the presence of antibody to hepatitis B core antigen (anti-HBc) in the blood of apparently healthy individuals may not indicate the absence of circulating hepatitis B virus (HBV) and might be infectious. Despite the risk of HBV transmission, there has been no report from Ethiopia examining this issue; therefore, this study determined occult HBV infection (OBI) among isolated anti-HBc (IAHBc) HIV negative and HIV positive individuals on ART in eastern Ethiopia. A total of 306 IAHBc individuals were included in this study. DNA was extracted, amplified, and detected from plasma using a commercially available RealTime PCR platform (Abbott m2000rt) following the manufacturer's instructions. Data were entered into EPI Data version 3.1, cleaned, and analyzed using Stata version 13. Descriptive analysis was used to calculate prevalence, summarize sociodemographic data and other factors. From the 306 IAHBc individuals (184 HIV positive and 122 HIV negative) included in the study, 183 (59.8%) were female of which 142 (77.6%) were within the reproductive age group. DNA extraction, amplified and detection was conducted in 224 individuals. The overall OBI prevalence was 5.8% (5.6% in HIV negative and 6% in HIV positive) among the IAHBc individuals. The HBV DNA concentration among the occult hepatitis B individuals was < 200 IU/mL, indicating a true occult. This study reported the burden of OBI, which pauses a significant public health problem due to the high burden of HBV infection in the country. OBI may cause substantial risk of HBV transmission from blood transfusion, organ transplantation as well as vertical transmission as screening is solely dependent on HBsAg testing.
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Affiliation(s)
- Desalegn Admassu Ayana
- College of Health and Medical Sciences, Haramaya University, Haramaya, Ethiopia.
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
| | - A Mulu
- College of Health and Medical Sciences, Haramaya University, Haramaya, Ethiopia
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia
| | - A Mihret
- College of Health and Medical Sciences, Haramaya University, Haramaya, Ethiopia
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia
| | - B Seyoum
- College of Health and Medical Sciences, Haramaya University, Haramaya, Ethiopia
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia
| | - A Aseffa
- College of Health and Medical Sciences, Haramaya University, Haramaya, Ethiopia
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia
| | - R Howe
- College of Health and Medical Sciences, Haramaya University, Haramaya, Ethiopia
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia
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5
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Salpini R, Malagnino V, Piermatteo L, Mulas T, Alkhatib M, Scutari R, Teti E, Cerva C, Yu La Rosa K, Brugneti M, Bertoli A, Rossi B, Holzmayer V, Gersch J, Kuhns M, Cloherty G, Ceccherini-Silberstein F, Perno CF, Iannetta M, Andreoni M, Sarmati L, Svicher V. Cryptic HBV Replicative Activity Is Frequently Revealed in Anti-HBc-Positive/HBsAg-Negative Patients with HIV Infection by Highly Sensitive Molecular Assays, and Can Be Predicted by Integrating Classical and Novel Serological HBV Markers. Microorganisms 2020; 8:microorganisms8111819. [PMID: 33218205 PMCID: PMC7699270 DOI: 10.3390/microorganisms8111819] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 11/09/2020] [Accepted: 11/17/2020] [Indexed: 12/14/2022] Open
Abstract
The anti-HBc-positive/HBsAg-negative status is frequent in HIV-infection and correlates with poor survival. Here, by highly-sensitive assays, we evaluate cryptic HBV replication and factors correlated with its detection in 81 anti-HBc-positive/HBsAg-negative HIV-infected patients. Patients were treated for >12 months with HBV-active modern combined antiretroviral-therapy (cART) and had serum HBV-DNA < 20 IU/mL by commercial Real-Time PCR. Serum HBV-DNA was quantified by droplet digital PCR, serum HBV-RNA by an Abbott research assay, and anti-HBc titer (proposed to infer intrahepatic cccDNA) by Lumipulse/Fujirebio. Cryptic serum HBV-DNA was detected in 29.6% of patients (median (IQR): 4(1-15) IU/mL) and serum HBV-RNA in 3.7% of patients despite HBsAg-negativity and HBV-active cART. Notably, cryptic serum HBV-DNA correlated with an advanced CDC-stage (p = 0.01) and a lower anti-HBs titer (p = 0.05), while serum HBV-RNA correlated with lower nadir CD4+ cell-count (p = 0.01). By analyzing serological HBV-markers, the combination of anti-HBs < 50 mIU/mL (indicating lower immune response) plus anti-HBc > 15COI (reflecting higher HBV replicative activity) was predictive of cryptic serum HBV-DNA (OR: 4.7(1.1-21.7), p = 0.046, PPV = 62.5%, and NPV = 72%). In conclusion, cryptic HBV-replication (not detected by classical assays) characterizes a conspicuous set of anti-HBc-positive HIV-infected patients despite HBsAg-negativity and HBV-active combined antiretroviral therapy (cART). The integration of classical and novel markers may help identify patients with cryptic HBV-replication, thus optimizing the monitoring of anti-HBc-positive/HBsAg-negative HIV-infected patients.
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Affiliation(s)
- Romina Salpini
- Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy; (R.S.); (L.P.); mohammad-- (M.A.); (R.S.); (K.Y.L.R.); (M.B.); (A.B.); (F.C.-S.)
| | - Vincenzo Malagnino
- Clinic of Infectious Diseases, Tor Vergata University Hospital, 00133 Rome, Italy; (V.M.); (T.M.); (E.T.); (C.C.); (B.R.); (M.I.); (M.A.); (L.S.)
| | - Lorenzo Piermatteo
- Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy; (R.S.); (L.P.); mohammad-- (M.A.); (R.S.); (K.Y.L.R.); (M.B.); (A.B.); (F.C.-S.)
| | - Tiziana Mulas
- Clinic of Infectious Diseases, Tor Vergata University Hospital, 00133 Rome, Italy; (V.M.); (T.M.); (E.T.); (C.C.); (B.R.); (M.I.); (M.A.); (L.S.)
| | - Mohammad Alkhatib
- Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy; (R.S.); (L.P.); mohammad-- (M.A.); (R.S.); (K.Y.L.R.); (M.B.); (A.B.); (F.C.-S.)
| | - Rossana Scutari
- Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy; (R.S.); (L.P.); mohammad-- (M.A.); (R.S.); (K.Y.L.R.); (M.B.); (A.B.); (F.C.-S.)
| | - Elisabetta Teti
- Clinic of Infectious Diseases, Tor Vergata University Hospital, 00133 Rome, Italy; (V.M.); (T.M.); (E.T.); (C.C.); (B.R.); (M.I.); (M.A.); (L.S.)
| | - Carlotta Cerva
- Clinic of Infectious Diseases, Tor Vergata University Hospital, 00133 Rome, Italy; (V.M.); (T.M.); (E.T.); (C.C.); (B.R.); (M.I.); (M.A.); (L.S.)
| | - Katia Yu La Rosa
- Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy; (R.S.); (L.P.); mohammad-- (M.A.); (R.S.); (K.Y.L.R.); (M.B.); (A.B.); (F.C.-S.)
| | - Marta Brugneti
- Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy; (R.S.); (L.P.); mohammad-- (M.A.); (R.S.); (K.Y.L.R.); (M.B.); (A.B.); (F.C.-S.)
| | - Ada Bertoli
- Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy; (R.S.); (L.P.); mohammad-- (M.A.); (R.S.); (K.Y.L.R.); (M.B.); (A.B.); (F.C.-S.)
| | - Benedetta Rossi
- Clinic of Infectious Diseases, Tor Vergata University Hospital, 00133 Rome, Italy; (V.M.); (T.M.); (E.T.); (C.C.); (B.R.); (M.I.); (M.A.); (L.S.)
| | - Vera Holzmayer
- Abbott Molecular, Des Plaines, IL 60018-3315, USA; (V.H.); (J.G.); (M.K.); (G.C.)
| | - Jeffrey Gersch
- Abbott Molecular, Des Plaines, IL 60018-3315, USA; (V.H.); (J.G.); (M.K.); (G.C.)
| | - Mary Kuhns
- Abbott Molecular, Des Plaines, IL 60018-3315, USA; (V.H.); (J.G.); (M.K.); (G.C.)
| | - Gavin Cloherty
- Abbott Molecular, Des Plaines, IL 60018-3315, USA; (V.H.); (J.G.); (M.K.); (G.C.)
| | - Francesca Ceccherini-Silberstein
- Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy; (R.S.); (L.P.); mohammad-- (M.A.); (R.S.); (K.Y.L.R.); (M.B.); (A.B.); (F.C.-S.)
| | - Carlo-Federico Perno
- Microbiology and Immunology Diagnostics, Ospedale Pediatrico Bambino Gesù, 00165 Rome, Italy;
| | - Marco Iannetta
- Clinic of Infectious Diseases, Tor Vergata University Hospital, 00133 Rome, Italy; (V.M.); (T.M.); (E.T.); (C.C.); (B.R.); (M.I.); (M.A.); (L.S.)
| | - Massimo Andreoni
- Clinic of Infectious Diseases, Tor Vergata University Hospital, 00133 Rome, Italy; (V.M.); (T.M.); (E.T.); (C.C.); (B.R.); (M.I.); (M.A.); (L.S.)
| | - Loredana Sarmati
- Clinic of Infectious Diseases, Tor Vergata University Hospital, 00133 Rome, Italy; (V.M.); (T.M.); (E.T.); (C.C.); (B.R.); (M.I.); (M.A.); (L.S.)
| | - Valentina Svicher
- Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy; (R.S.); (L.P.); mohammad-- (M.A.); (R.S.); (K.Y.L.R.); (M.B.); (A.B.); (F.C.-S.)
- Correspondence:
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6
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Mitsumoto-Kaseida F, Murata M, Takayama K, Toyoda K, Ogawa E, Furusyo N, Hayashi J. Prevalence and characteristics of occult hepatitis B virus infection in Japanese human immunodeficiency virus-infected patients. J Infect Chemother 2019; 26:28-32. [PMID: 31279522 DOI: 10.1016/j.jiac.2019.06.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2019] [Revised: 06/05/2019] [Accepted: 06/10/2019] [Indexed: 02/07/2023]
Abstract
Occult hepatitis B virus (HBV) infection (OBI) is hepatitis B surface antigen (HBsAg) negative but with detectable HBV DNA. Although HIV infection has been reported to be a risk factor for OBI, the prevalence and clinical features of OBI in Japanese HIV infected patients have not been documented. This retrospective, single-center study was conducted to determine the prevalence and characteristic of OBI in Japanese antiretroviral therapy (ART) naïve HIV infected patients. OBI was defined as the presence of serum HBV DNA but without detectable HBsAg. Of the 147 ART naïve HIV infected patients, OBI was detected in 9 (6.1%) patients; 2 (4.3%) of 47 with both anti-HBs and anti-HBc positive, 6 (27.3%) of 22 with anti-HBc alone, and 1 (2.0%) of 50 with both anti-HBs and anti-HBc negative. The mean HBV DNA level was low at 28.7 ± 18.2 IU/mL. The proportion of OBI patients with anti-HBc alone was significantly higher than that of non-OBI patients (66.7% vs 14.5%, P = 0.001). In addition, the prevalence of AIDS (acquired immunodeficiency syndrome)-defining illnesses in the OBI group was significantly higher than in the non-OBI group (77.8% vs 35.5%, P = 0.001). No significant difference was found in the CD4 count or alanine aminotransferase levels of these two groups. This is the first study to reveal the prevalence and clinical features of OBI in Japanese HIV-infected patients. The persistence of anti-HBc alone and AIDS-defining illnesses were associated with the occurrence of OBI in these patients.
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Affiliation(s)
- Fujiko Mitsumoto-Kaseida
- Department of General Internal Medicine, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
| | - Masayuki Murata
- Department of General Internal Medicine, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
| | - Koji Takayama
- Department of General Internal Medicine, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
| | - Kazuhiro Toyoda
- Department of General Internal Medicine, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
| | - Eiichi Ogawa
- Department of General Internal Medicine, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
| | - Norihiro Furusyo
- Department of General Internal Medicine, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
| | - Jun Hayashi
- Kyushu General Medicine Center, Haradoi Hospital, 6-40-8 Aoba, Higashi-ku, Fukuoka, 813-8588, Japan.
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7
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Abdullahi A, Fopoussi OM, Torimiro J, Atkins M, Kouanfack C, Geretti AM. Hepatitis B Virus (HBV) Infection and Re-activation During Nucleos(t)ide Reverse Transcriptase Inhibitor-Sparing Antiretroviral Therapy in a High-HBV Endemicity Setting. Open Forum Infect Dis 2018; 5:ofy251. [PMID: 30377627 PMCID: PMC6201150 DOI: 10.1093/ofid/ofy251] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Accepted: 10/02/2018] [Indexed: 12/19/2022] Open
Abstract
Background We monitored the evolution of markers of hepatitis B virus (HBV) infection in virologically suppressed HIV-positive patients switching to nucleoside reverse transcriptase inhibitor (NRTI)–sparing antiretroviral therapy within a randomized trial in Cameroon. Methods HBV surface antigen (HBsAg), HBV DNA, and antibodies against surface (anti-HBs), core (total anti-HBc), and e-antigen (anti-HBe) were measured retrospectively in samples collected at study entry and over 48 weeks after NRTI discontinuation. Results Participants (n = 80, 75% females) had a plasma HIV-1 RNA <60 copies/mL, a median CD4 count of 466 cells/mm3, and undetectable HBsAg and HBV DNA at study entry. After NRTI discontinuation, 3/20 (15.0%) anti-HBc-negative patients showed evidence indicative or suggestive of incident HBV infection (163 cases/1000 person-years); 6/60 (10.0%) anti-HBc-positive patients showed evidence indicative or suggestive of HBV reactivation (109 cases/1000 person-years). In one case of reactivation, anti-HBs increased from 14 to >1000 IU/L; sequencing showed HBV genotype A3 and 3 escape mutations in surface (Y100C, K122R, Y161FY). Alongside new-onset detection of HBsAg or HBV DNA, 1 patient experienced acute hepatitis and 6 patients experienced mild or marginal increases in serum transaminase levels. Conclusions Evolving treatment strategies for sub-Saharan Africa must be accompanied by the formulation and implementation of policy to guide appropriate assessment and management of HBV status.
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Affiliation(s)
- Adam Abdullahi
- Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom
| | - Olga Mafotsing Fopoussi
- Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.,Chantal Biya International Reference Centre for Research on HIV/AIDS Prevention and Management (CIRCB), Yaoundé, Cameroon
| | - Judith Torimiro
- Chantal Biya International Reference Centre for Research on HIV/AIDS Prevention and Management (CIRCB), Yaoundé, Cameroon
| | - Mark Atkins
- Department of Microbiology, Frimley Park Hospital NHS Foundation Trust, Frimley, United Kingdom
| | - Charles Kouanfack
- Day Hospital, Yaoundé Central Hospital, Ministry of Public Health, Yaoundé, Cameroon
| | - Anna Maria Geretti
- Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom
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8
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Geretti AM, Brook G, Cameron C, Chadwick D, French N, Heyderman R, Ho A, Hunter M, Ladhani S, Lawton M, MacMahon E, McSorley J, Pozniak A, Rodger A. British HIV Association Guidelines on the Use of Vaccines in HIV-Positive Adults 2015. HIV Med 2018; 17 Suppl 3:s2-s81. [PMID: 27568789 DOI: 10.1111/hiv.12424] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Anna Maria Geretti
- Institute of Infection and Global Health, University of Liverpool, Liverpool, UK
| | | | | | | | | | | | | | | | | | - Mark Lawton
- Royal Liverpool University Hospital, Liverpool, UK
| | - Eithne MacMahon
- Guy's & St Thomas' NHS Foundation Trust, London, UK.,King's College London, London, UK
| | | | - Anton Pozniak
- Chelsea and Westminster Hospital, NHS Foundation Trust, London, UK
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9
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Tajik Z, Bokharaei-Salim F, Ghorbani S, Keyvani H, Esghaei M, Monavari SH, Ataei-Pirkooh A, Garshasbi S, Donyavi T, Fakhim A. Detection of HBV genome in the plasma and peripheral blood mononuclear cells of Iranian HBsAg negative patients with HIV infection: occult HBV infection. Arch Virol 2018; 163:1559-1566. [PMID: 29476259 DOI: 10.1007/s00705-018-3740-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Accepted: 12/28/2017] [Indexed: 01/05/2023]
Abstract
The presence of hepatitis B virus (HBV) DNA in the absence of traceable hepatitis B surface antigen (HBsAg) in the plasma specimen of patients is defined as occult HBV infection (OBI). This study aimed to detect HBV-DNA in the plasma and peripheral blood mononuclear cells (PBMCs) of Iranian HBsAg negative patients with human immunodeficiency virus (HIV) infection. This cross-sectional study was conducted on 172 patients with HIV infection from September 2015 to August 2017. The patients were tested for serological parameters (HBsAg, HBcAb, HBeAg and HBeAb) against HBV infection. Moreover, they were tested for HBV viral load (using COBAS TaqMan 48 Kit, Roche, USA) in plasma and the presence of the HBV genome in PBMC specimens using real-time PCR. The mean age of the patients was 35.4 ± 13.4 years. Of the 172 studied patients, 109 (63.4%) were male. In this study, 151 (87.8%) patients were negative for HBsAg, 111 (64.5%) patients were negative for all HBV infection serological markers, 9 (5.2%) patients were only positive for HBsAg and 29 (16.9%) patients were only positive for HBcAb. Moreover, five (3.3%) patients with HBsAg negative had OBI (in the plasma sample of four patients and PBMC specimens of all five patients, HBV-DNA was detected). The present study revealed that 3.3% of the patients with HIV infection had occult HBV infection. Presumably, designing prospective studies to identify this infection in patients with HIV infection is informative and valuable.
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Affiliation(s)
- Zahra Tajik
- HIV Laboratory of National Center, Iran University of Medical Sciences, Tehran, Iran
| | - Farah Bokharaei-Salim
- HIV Laboratory of National Center, Iran University of Medical Sciences, Tehran, Iran. .,Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Saied Ghorbani
- Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Hossein Keyvani
- Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Maryam Esghaei
- Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | | | - Angila Ataei-Pirkooh
- Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Saba Garshasbi
- HIV Laboratory of National Center, Iran University of Medical Sciences, Tehran, Iran
| | - Tahereh Donyavi
- HIV Laboratory of National Center, Iran University of Medical Sciences, Tehran, Iran
| | - Atousa Fakhim
- Department of Architectural Engineering, Faculty of Engineering, Islamic Azad University, South Tehran Branch, Tehran, Iran
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10
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First report of occult hepatitis B infection among ART naïve HIV seropositive individuals in Maputo, Mozambique. PLoS One 2018; 13:e0190775. [PMID: 29320552 PMCID: PMC5761887 DOI: 10.1371/journal.pone.0190775] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Accepted: 12/20/2017] [Indexed: 12/21/2022] Open
Abstract
Background The prevalence of hepatitis B virus (HBV) infection and human immunodeficiency virus (HIV) infection in Mozambique is one of the highest in the world, though in spite of this the prevalence of occult hepatitis B infection (OBI) is unknown. Objectives This study was conducted with the aim to investigate the prevalence of OBI and frequency of isolated hepatitis B core antibody (anti-HBc alone) among antiretroviral (ART) naïve HIV-positive patients in Mozambique. Methods A cross-sectional study was conducted in two health facilities within Maputo city. All ART-naive HIV seropositive patients attending outpatient clinics between June and October 2012 were consecutively enrolled. Blood samples were drawn from each participant and used for serological measurement of HBV surface antigen (HBsAg), antibodies against HBV surface antigen (anti-HBs) and antibodies against core antigen (anti-HBc) using ELISA. Quantification of HBV DNA was performed by real time PCR. A questionnaire was used to obtain demographics and clinical data. Results Of the 518 ART-naive HIV-positive subjects enrolled in the study, 90.9% (471/518) were HBsAg negative. Among HBsAg negative, 45.2% (213/471) had isolated anti-HBc antibodies, and the frequency of OBI among patients with anti-HBc alone was 8.3% (17/206). OBI was not correlated either with CD4+ T cells count or transaminases levels. A total of 11.8% of patients with OBI presented elevated HBV DNA level. Frequency of individuals with APRI score > 2 and FIB-4 score > 3.25 was higher in patients with OBI as compared not exposed, immune and anti-HBc alone patients. Conclusion Our data demonstrate for the first time that OBI is prevalent among HIV patients in Mozambique, and will be missed using the commonly available serological assays that measures HBsAg.
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11
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Ryan K, Anderson M, Gyurova I, Ambroggio L, Moyo S, Sebunya T, Makhema J, Marlink R, Essex M, Musonda R, Gaseitsiwe S, Blackard JT. High Rates of Occult Hepatitis B Virus Infection in HIV-Positive Individuals Initiating Antiretroviral Therapy in Botswana. Open Forum Infect Dis 2017; 4:ofx195. [PMID: 29062862 PMCID: PMC5641381 DOI: 10.1093/ofid/ofx195] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Accepted: 09/12/2017] [Indexed: 12/16/2022] Open
Abstract
Background Hepatitis B surface antigen (HBsAg)–negative but hepatitis B virus (HBV) DNA-positive infection—known as occult hepatitis B infection (OBI)—occurs in 1% to >15% of HIV-positive individuals in the United States and South Africa, respectively. However, there are no data on OBI from Botswana, a country known to be hyperendemic for chronic HBV infection and to have a significant HIV burden. Methods Two hundred seventy-two adults enrolled in an HIV treatment study of tenofovir/emtricitabine as the nucleoside backbone who were previously determined to be HBsAg negative were tested for HBV DNA at baseline and 1 year after initiation of highly active antiretroviral therapy (HAART). Results HBV DNA was detected in 72 of 272 (26.5%). Six individuals (8.3%) had HBV DNA levels greater than 200 IU/mL, and the highest viral load was 3280 IU/mL. Of 65 participants with OBI evaluated at 12 months after initiating HAART, only 1 (1.5%) had detectable HBV DNA. Conclusions Occult HBV infection is quite common in HIV-infected patients in Botswana, although its impact on the course of HIV disease progression is unknown. The suppression of occult HBV DNA levels by tenofovir/emtricitabine suggests an effective therapeutic option, although the long-term suppressive abilities remain unstudied.
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Affiliation(s)
- Kathleen Ryan
- University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Motswedi Anderson
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.,Department of Biological Sciences, University of Botswana, Gaborone, Botswana
| | - Ivayla Gyurova
- University of Cincinnati College of Medicine, Cincinnati, Ohio
| | | | - Sikhulile Moyo
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.,Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Teresa Sebunya
- Department of Biological Sciences, University of Botswana, Gaborone, Botswana
| | - Joseph Makhema
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.,Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Richard Marlink
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.,Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Max Essex
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.,Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Rosemary Musonda
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.,Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Simani Gaseitsiwe
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.,Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
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12
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Saha D, Pal A, Sarkar N, Das D, Blackard JT, Guha SK, Saha B, Chakravarty R. Occult hepatitis B virus infection in HIV positive patients at a tertiary healthcare unit in eastern India. PLoS One 2017; 12:e0179035. [PMID: 28591184 PMCID: PMC5462430 DOI: 10.1371/journal.pone.0179035] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2017] [Accepted: 05/23/2017] [Indexed: 12/13/2022] Open
Abstract
Occult HBV infection (OBI), defined by the presence of HBV DNA in absence of hepatitis B surface antigen (HBsAg), is a significant concern in the HIV-infected population. Of 441 HIV+/HBsAg- patients analyzed, the overall prevalence of OBI was 6.3% (28/441). OBI was identified in 21 anti-HBc positives (17.8%), as well as among those who lacked any HBV-specific serological markers (2.2%). Comparison with HIV/HBV co-infection revealed that the levels of CD4, ALT, and HBV DNA were significantly lower during occult infection. Discrete differences were also observed with respect to quasispecies divergence. Additionally, subgenotype D1 was most frequent in occult infection, while D2 was widespread during chronic infection. The majority (~90%) of occult D1 sequences had the sQ129R mutation in the surface gene. This study highlights several distinct features of OBI in India and underscores the need for additional HBV DNA screening in HIV-positive individuals.
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Affiliation(s)
- Debraj Saha
- ICMR Virus Unit, Kolkata, ID & BG Hospital Campus, Kolkata, West Bengal, India
| | - Ananya Pal
- ICMR Virus Unit, Kolkata, ID & BG Hospital Campus, Kolkata, West Bengal, India
| | - Neelakshi Sarkar
- ICMR Virus Unit, Kolkata, ID & BG Hospital Campus, Kolkata, West Bengal, India
| | - Dipanwita Das
- ICMR Virus Unit, Kolkata, ID & BG Hospital Campus, Kolkata, West Bengal, India
| | - Jason T. Blackard
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America
| | | | - Bibhuti Saha
- Calcutta School of Tropical Medicine, Kolkata, West Bengal, India
| | - Runu Chakravarty
- ICMR Virus Unit, Kolkata, ID & BG Hospital Campus, Kolkata, West Bengal, India
- * E-mail:
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13
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Mohraz M, Jafari R, Poortahmasebi V, Sadeghi A, Hajabdolbaghi M, Rasoolinejad M, Forooghi M, Norouzi M, Poorebrahim M, Khamseh A, Karkhaneh M, Alavian SM, Ebrahimian A, Jazayeri SM. Molecular analysis of occult hepatitis B infection among Iranian HIV-positive patients. Future Virol 2016. [DOI: 10.2217/fvl-2016-0032] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Aim: The aims of this study were to find out the prevalence of occult hepatitis B infection (OBI) in HIV-1 patients, as well as to analyze the mutational patterns of OBI-positive individuals. Materials & methods: 172 HBsAg-negative, HIV-1-positive patients were selected according to data extracted from questionnaires. HBV serologic and molecular assays were performed. An extensive mutational analysis was applied using direct sequencing on HBsAg. Results: Thirty-one samples (18%) were OBI positive. Among 24 available OBI-positive samples, 17 (71%) contained at least one mutation only within ‘a’ determinant region of HBsAg. A stretch of mutations was found between amino acid positions 121 and 136. The physicochemical properties of individual amino acid substitutions and their potential impacts on 3D structure of ‘a’ determinant mutants were also determined. Conclusion: HBV serologic assays are not reliable markers to exclude occult HBV infection in HIV-positive patients.
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Affiliation(s)
- Minoo Mohraz
- Iranian Research Center for HIV AIDS, High Risk Reduction Institute, Tehran, Iran
| | - Rezvaneh Jafari
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Vahdat Poortahmasebi
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Ahmadreza Sadeghi
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Mehrnaz Rasoolinejad
- Iranian Research Center for HIV AIDS, High Risk Reduction Institute, Tehran, Iran
| | - Maryam Forooghi
- Iranian Research Center for HIV AIDS, High Risk Reduction Institute, Tehran, Iran
| | - Mehdi Norouzi
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Mansour Poorebrahim
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Azam Khamseh
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Masoud Karkhaneh
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed Moayed Alavian
- Middle East Liver Disease (MELD) Center, No 178, Sepahboud Gharanee St. Tehran 1598976516, Iran
| | - Arefeh Ebrahimian
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
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14
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Profile and prevalence of HBV among HIV affected individuals attending the largest public HIV care center in India. Virusdisease 2016; 27:215-219. [PMID: 28466031 DOI: 10.1007/s13337-016-0323-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2016] [Accepted: 05/20/2016] [Indexed: 01/24/2023] Open
Abstract
A large number of people living with HIV/AIDS residing in HBV endemic regions such as in India are highly susceptible to acquire co-infections like HBV but also transmit them to other due to their high risk behaviours. The present study aimed to estimate HBV prevalence and distribution of various HBV serological markers among HIV infected individuals. This cross sectional survey covered HIV infected individuals attending the largest HIV care center in India. Socio-demographic details and blood samples to screen for HBV seromarkers using commercial ELISA kits were collected. Among 1160 HIV infected patients, prevalence of HBcAb, HBsAb, HBsAg and HBeAg was 66, 29.4, 16.6 and 5.8 % respectively. Overall, 28.9 % individuals had no evidence of any of the four markers, indicating lack of previous exposure and future risk of acquiring HBV infection. Presence of anti-HBsAg in a mere 0.9 % of individuals reflected low levels HBV vaccine conferred immunity which could be due to poor HBV vaccine coverage in this high risk population. With high prevalence and evidence of exposure to HBV as well as considering the growing literature on increase in hepatic complications in HIV-HBV co-infected individuals, the need for mandatory HBV screening of all HIV infected individuals cannot be over-emphasised. The policy makers and HIV programme managers must consider HBV vaccination for newly detected HBV naive HIV infected individuals and also focus on creating public awareness on HBV and HIV prevention.
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15
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Maldonado-Rodriguez A, Cevallos AM, Rojas-Montes O, Enriquez-Navarro K, Alvarez-Muñoz MT, Lira R. Occult hepatitis B virus co-infection in human immunodeficiency virus-positive patients: A review of prevalence, diagnosis and clinical significance. World J Hepatol 2015; 7:253-260. [PMID: 25729480 PMCID: PMC4342607 DOI: 10.4254/wjh.v7.i2.253] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2014] [Revised: 10/22/2014] [Accepted: 11/19/2014] [Indexed: 02/06/2023] Open
Abstract
The prevalence of human immunodeficiency virus (HIV) and hepatitis B virus (HBV) co-infection is high as they share similar mechanisms of transmission. The development and widespread use of highly sensitive tests for HBV diagnosis has demonstrated that a significant proportion of apparently healthy individuals with evidence of exposure to HBV continue to carry fully functional HBV DNA in their hepatocytes, a situation that predisposes them to the development of progressive liver disease and hepatocellular carcinoma. The presence of co-infections frequently influences the natural evolution of each of the participating infections present by either facilitating their virulence or competing for resources. Furthermore, the drugs used to treat these infections may also contribute to changes in the natural course of these infections, making the analysis of the impact of co-infection more difficult. The majority of studies has examined the impact of HIV on overt chronic hepatitis B, finding that co-infection carries an increased risk of progressive liver disease and the development of hepatocellular carcinoma. Although the effect of HIV on the natural history of occult hepatitis B infection (OBI) has not been fully assessed, all available data suggest a persisting risk of repeated flares of hepatitis and progressive liver disease. We describe studies regarding the diagnosis, prevalence and clinical significance of OBI in HIV-positive patients in this short review. Discrepancies in worldwide prevalence show the urgent need for the standardization of diagnostic criteria, as established by the Taormina statements. Ideally, standardized protocols for testing should be employed to enable the comparison of data from different groups. Additional studies are needed to define the differences in risk for OBI without HIV and in HIV-HBV co-infected patients with or without overt disease.
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16
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Bautista-Amorocho H, Castellanos-Domínguez YZ, Rodríguez-Villamizar LA, Velandia-Cruz SA, Becerra-Peña JA, Farfán-García AE. Epidemiology, risk factors and genotypes of HBV in HIV-infected patients in the northeast region of Colombia: high prevalence of occult hepatitis B and F3 subgenotype dominance. PLoS One 2014; 9:e114272. [PMID: 25462190 PMCID: PMC4252145 DOI: 10.1371/journal.pone.0114272] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2014] [Accepted: 11/09/2014] [Indexed: 12/18/2022] Open
Abstract
INTRODUCTION Chronic hepatitis B virus (HBV) infection is an increasing cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected individuals. HIV-positive patients are commonly co-infected with HBV due to shared routes of transmission. OBJECTIVES Our aim was to determine the risk factors, prevalence, genotypes, and mutations of the Surface S gene of HBV, and occult hepatitis B infection (OBI) among patients infected with HIV in a northeastern Colombian city. METHODS A cross-sectional study was conducted with 275 HIV-positive patients attending an outpatient clinic in Bucaramanga, Colombia during 2009-2010. Blood samples were collected and screened for serological markers of HBV (anti-HBs, anti-HBc and HBsAg) through ELISA assay. Regardless of their serological profile, all samples were tested for the HBV S gene by nested-PCR and HBV genotypes were determined by phylogenetic inference. Clinical records were used to examine demographic, clinical, virological, immunological and antiretroviral therapy (ART) variables of HIV infection. RESULTS Participants were on average 37±11 years old and 65.1% male. The prevalence of HIV-HBV coinfection was 12% (95%CI 8.4-16.4) of which 3.3% had active HBV infection and 8.7% OBI. The prevalence of HIV-HBV coinfection was associated with AIDS stage and ART treatment. Sequence analysis identified genotype F, subgenotype F3 in 93.8% of patients and genotype A in 6.2% of patients. A C149R mutation, which may have resulted from failure in HBsAg detection, was found in one patient with OBI. CONCLUSIONS The present study found a high prevalence of HIV-HBV coinfection with an incidence of OBI 2.6-fold higher compared to active HBV infection. These findings suggest including HBV DNA testing to detect OBI in addition to screening for HBV serological markers in HIV patients.
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Affiliation(s)
- Henry Bautista-Amorocho
- University of Santander (UDES), Bacteriology and Clinical Laboratory Program, Department of Health Sciences, CliniUDES Research Group, Laboratory for Biomedical and Biotechnological Research (LBBR) Bucaramanga, Santander, Colombia
- * E-mail:
| | - Yeny Zulay Castellanos-Domínguez
- University of Santander (UDES), Bacteriology and Clinical Laboratory Program, Department of Health Sciences, CliniUDES Research Group, Laboratory for Biomedical and Biotechnological Research (LBBR) Bucaramanga, Santander, Colombia
| | - Laura Andrea Rodríguez-Villamizar
- Industrial University of Santander (UIS), Department of Public Health, School of Medicine, Research Group on Demography, Public Health and Health Systems (GUINDESS), Bucaramanga, Santander, Colombia
| | - Sindi Alejandra Velandia-Cruz
- University of Santander (UDES), Bacteriology and Clinical Laboratory Program, Department of Health Sciences, CliniUDES Research Group, Laboratory for Biomedical and Biotechnological Research (LBBR) Bucaramanga, Santander, Colombia
| | - Jeysson Andrey Becerra-Peña
- University of Santander (UDES), Bacteriology and Clinical Laboratory Program, Department of Health Sciences, CliniUDES Research Group, Laboratory for Biomedical and Biotechnological Research (LBBR) Bucaramanga, Santander, Colombia
| | - Ana Elvira Farfán-García
- University of Santander (UDES), Bacteriology and Clinical Laboratory Program, Department of Health Sciences, CliniUDES Research Group, Laboratory for Biomedical and Biotechnological Research (LBBR) Bucaramanga, Santander, Colombia
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17
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Alvarez-Muñoz MT, Maldonado-Rodriguez A, Rojas-Montes O, Torres-Ibarra R, Gutierrez-Escolano F, Vazquez-Rosales G, Gomez A, Muñoz O, Torres J, Lira R. Occult hepatitis B virus infection among Mexican human immunodeficiency virus-1-infected patients. World J Gastroenterol 2014; 20:13530-13537. [PMID: 25309083 PMCID: PMC4188904 DOI: 10.3748/wjg.v20.i37.13530] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Revised: 04/30/2014] [Accepted: 05/26/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the frequency of occult hepatitis B infection (OHBI) in a group of human immunodeficiency virus (HIV)-1+/ hepatitis B surface antigen negative (HBsAg)- patients from Mexico.
METHODS: We investigated the presence of OHBI in 49 HIV-1+/HBsAg- patients. Hepatitis B virus (HBV) DNA was analyzed using nested PCR to amplify the Core (C) region and by real-time PCR to amplify a region of the S and X genes. The possible associations between the variables and OHBI were investigated using Pearson’s χ2 and/or Fisher’s exact test.
RESULTS: We found that the frequency of OHBI was 49% among the group of 49 HIV-1+/HBsAg- patients studied. The presence of OHBI was significantly associated with the HIV-1 RNA viral load [odds ratio (OR) = 8.75; P = 0.001; 95%CI: 2.26-33.79] and with HIV-antiretroviral treatment with drugs that interfere with HBV replication (lamivudine, tenofovir or emtricitabine) (OR = 0.25; P = 0.05; 95%CI: 0.08-1.05).
CONCLUSION: The OHBI frequency is high among 49 Mexican HIV-1+/HBsAg- patients and it was more frequent in patients with detectable HIV RNA, and less frequent in patients who are undergoing HIV-ARV treatment with drugs active against HBV.
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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; 6:384-393. [PMID: 25018849 PMCID: PMC4081613 DOI: 10.4254/wjh.v6.i6.384] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2013] [Revised: 03/16/2014] [Accepted: 06/03/2014] [Indexed: 02/06/2023] Open
Abstract
Occult hepatitis B infection (OBI), is characterized by low level hepatitis B virus (HBV) DNA in circulating blood and/or liver tissue. In clinical practice the presence of antibody to hepatitis B core antigen in hepatitis B surface antigen (HBsAg)-/anti-HBs-negative subjects is considered indicative of OBI. OBI is mostly observed in the window period of acute HBV infection in blood donors and in recipients of blood and blood products, in hepatitis C virus chronic carriers, in patients under pharmacological immunosuppression, and in those with immunodepression due to HIV infection or cancer. Reactivation of OBI mostly occurs in anti-HIV-positive subjects, in patients treated with immunosuppressive therapy in onco-hematological settings, in patients who undergo hematopoietic stem cell transplantation, in those treated with anti-CD20 or anti-CD52 monoclonal antibody, or anti-tumor necrosis factors antibody for rheumatological diseases, or chemotherapy for solid tumors. Under these conditions the mortality rate for hepatic failure or progression of the underlying disease due to discontinuation of specific treatment can reach 20%. For patients with OBI, prophylaxis with nucleot(s)ide analogues should be based on the HBV serological markers, the underlying diseases and the type of immunosuppressive treatment. Lamivudine prophylaxis is indicated in hemopoietic stem cell transplantation and in onco-hematological diseases when high dose corticosteroids and rituximab are used; monitoring may be indicated when rituximab-sparing schedules are used, but early treatment should be applied as soon as HBsAg becomes detectable. This review article presents an up-to-date evaluation of the current knowledge on OBI.
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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. [PMID: 25018849 DOI: 10.4254/wjh.v6i6.384] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Occult hepatitis B infection (OBI), is characterized by low level hepatitis B virus (HBV) DNA in circulating blood and/or liver tissue. In clinical practice the presence of antibody to hepatitis B core antigen in hepatitis B surface antigen (HBsAg)-/anti-HBs-negative subjects is considered indicative of OBI. OBI is mostly observed in the window period of acute HBV infection in blood donors and in recipients of blood and blood products, in hepatitis C virus chronic carriers, in patients under pharmacological immunosuppression, and in those with immunodepression due to HIV infection or cancer. Reactivation of OBI mostly occurs in anti-HIV-positive subjects, in patients treated with immunosuppressive therapy in onco-hematological settings, in patients who undergo hematopoietic stem cell transplantation, in those treated with anti-CD20 or anti-CD52 monoclonal antibody, or anti-tumor necrosis factors antibody for rheumatological diseases, or chemotherapy for solid tumors. Under these conditions the mortality rate for hepatic failure or progression of the underlying disease due to discontinuation of specific treatment can reach 20%. For patients with OBI, prophylaxis with nucleot(s)ide analogues should be based on the HBV serological markers, the underlying diseases and the type of immunosuppressive treatment. Lamivudine prophylaxis is indicated in hemopoietic stem cell transplantation and in onco-hematological diseases when high dose corticosteroids and rituximab are used; monitoring may be indicated when rituximab-sparing schedules are used, but early treatment should be applied as soon as HBsAg becomes detectable. This review article presents an up-to-date evaluation of the current knowledge on OBI.
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Affiliation(s)
- Evangelista Sagnelli
- Evangelista Sagnelli, Mariantonietta Pisaturo, Salvatore Martini, Pietro Filippini, Nicola Coppola, Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, 80131 Naples, Italy
| | - Mariantonietta Pisaturo
- Evangelista Sagnelli, Mariantonietta Pisaturo, Salvatore Martini, Pietro Filippini, Nicola Coppola, Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, 80131 Naples, Italy
| | - Salvatore Martini
- Evangelista Sagnelli, Mariantonietta Pisaturo, Salvatore Martini, Pietro Filippini, Nicola Coppola, Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, 80131 Naples, Italy
| | - Pietro Filippini
- Evangelista Sagnelli, Mariantonietta Pisaturo, Salvatore Martini, Pietro Filippini, Nicola Coppola, Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, 80131 Naples, Italy
| | - Caterina Sagnelli
- Evangelista Sagnelli, Mariantonietta Pisaturo, Salvatore Martini, Pietro Filippini, Nicola Coppola, Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, 80131 Naples, Italy
| | - Nicola Coppola
- Evangelista Sagnelli, Mariantonietta Pisaturo, Salvatore Martini, Pietro Filippini, Nicola Coppola, Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, 80131 Naples, Italy
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Chadwick D, Doyle T, Ellis S, Price D, Abbas I, Valappil M, Geretti AM. Occult hepatitis B virus coinfection in HIV-positive African migrants to the UK: a point prevalence study. HIV Med 2013; 15:189-92. [PMID: 24118868 PMCID: PMC4255299 DOI: 10.1111/hiv.12093] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/21/2013] [Indexed: 12/21/2022]
Abstract
Objectives Occult (surface antigen-negative/DNA-positive) hepatitis B virus (HBV) infection is common in areas of the world where HBV is endemic. The main objectives of this study were to determine the prevalence of occult HBV infection in HIV-infected African migrants to the UK and to determine factors associated with occult coinfection. Methods This anonymized point-prevalence study identified Africans attending three HIV clinics, focussing on patients naïve to antiretroviral therapy (ART). Stored blood samples were tested for HBV DNA. Prevalence was calculated in the entire cohort, as well as in subpopulations. Risk factors for occult HBV coinfection were identified using logistic regression analysis. Results Among 335 HIV-positive African migrants, the prevalence of occult HBV coinfection was 4.5% [95% confidence interval (CI) 2.8–7.4%] overall, and 6.5% (95% CI 3.9–10.6%) and 0.8% (95% CI 0.2–4.6%) in ART-naïve and ART-experienced patients, respectively. Among ART-naïve anti-HBV core (anti-HBc)-positive patients, the prevalence was 16.4% (95% CI 8.3–25.6%). The strongest predictor of occult coinfection was anti-HBc positivity [odds ratio (OR) 7.4; 95% CI 2.0–27.6]. Median HBV DNA and ALT levels were 54 IU/mL [interquartile range (IQR) 33–513 IU/mL] and 22 U/L (IQR 13–27 U/L), respectively. Conclusions Occult HBV coinfection remains under-diagnosed in African HIV-infected patients in the UK. Given the range of HBV DNA levels observed, further studies are warranted to determine its clinical significance and to guide screening strategies and ART selection in these patients.
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Affiliation(s)
- D Chadwick
- The James Cook University Hospital, Middlesbrough, UK
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Rusine J, Ondoa P, Asiimwe-Kateera B, Boer KR, Uwimana JM, Mukabayire O, Zaaijer H, Mugabekazi J, Reiss P, van de Wijgert JH. High seroprevalence of HBV and HCV infection in HIV-infected adults in Kigali, Rwanda. PLoS One 2013; 8:e63303. [PMID: 23717409 PMCID: PMC3661584 DOI: 10.1371/journal.pone.0063303] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2012] [Accepted: 04/01/2013] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Data on prevalence and incidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in Rwanda are scarce. METHODS HBV status was assessed at baseline and Month 12, and anti-HCV antibodies at baseline, in a prospective cohort study of HIV-infected patients in Kigali, Rwanda: 104 men and 114 women initiating antiretroviral therapy (ART) at baseline, and 200 women not yet eligible for ART. RESULTS Baseline prevalence of active HBV infection (HBsAg positive), past or occult HBV infection (anti-HBc positive and HBsAg negative) and anti-HCV was 5.2%, 42.9%, and 5.7%, respectively. The active HBV incidence rate was 4.2/1,000 person years (PY). In a multivariable logistic regression model using baseline data, participants with WHO stage 3 or 4 HIV disease were 4.19 times (95% CI 1.21-14.47) more likely to have active HBV infection, and older patients were more likely to have evidence of past exposure to HBV (aRR 1.03 per year; 95%CI 1.01-1.06). Older age was also positively associated with having anti-HCV antibodies (aOR 1.09; 95%CI 1.04-1.14) while having a higher baseline HIV viral load was negatively associated with HCV (aOR 0.60; 95% CI 0.40-0.98). The median CD4 increase during the first 12 months of ART was lower for those with active HBV infection or anti-HCV at baseline. Almost all participants (88%) with active HBV infection who were on ART were receiving lamivudine monotherapy for HBV. CONCLUSION HBV and HCV are common in HIV-infected patients in Rwanda. Regular HBsAg screening is needed to ensure that HIV-HBV co-infected patients receive an HBV-active ART regimen, and the prevalence of occult HBV infection should be determined. Improved access to HBV vaccination is recommended. Active HCV prevalence and incidence should be investigated further to determine whether HCV RNA PCR testing should be introduced in Rwanda.
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Affiliation(s)
- John Rusine
- Department of Global Health, Academic Medical Center, and Amsterdam Institute of Global Health and Development (AIGHD), Amsterdam, The Netherlands
- INTERACT Program, Kigali, Rwanda
- National Reference Laboratory, Kigali, Rwanda
| | - Pascale Ondoa
- Department of Global Health, Academic Medical Center, and Amsterdam Institute of Global Health and Development (AIGHD), Amsterdam, The Netherlands
| | | | - Kimberly R. Boer
- Department of Global Health, Academic Medical Center, and Amsterdam Institute of Global Health and Development (AIGHD), Amsterdam, The Netherlands
- INTERACT Program, Kigali, Rwanda
- Biomedical Research, Royal Tropical Institute, Amsterdam, The Netherlands
| | | | | | - Hans Zaaijer
- Department of Medical Microbiology, Academic Medical Center, Amsterdam, The Netherlands
| | | | - Peter Reiss
- Department of Global Health, Academic Medical Center, and Amsterdam Institute of Global Health and Development (AIGHD), Amsterdam, The Netherlands
| | - Janneke H. van de Wijgert
- Department of Global Health, Academic Medical Center, and Amsterdam Institute of Global Health and Development (AIGHD), Amsterdam, The Netherlands
- Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom
- * E-mail:
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Abstract
This study evaluated the outcome of first-line antiretroviral therapy among 35 Ghanaians with occult HBV/HIV co-infection, comparing them over 2 years to 120 patients with HBsAg+ HBV/HIV co-infection and 230 patients without HBV co-infection. Increases in CD4 cell count and BMI were similar, whereas elevations of hepatic transaminases were more frequent in both the occult HBV and HBsAg+ patients. Occult HBV/HIV co-infection appears not to impact adversely on response to antiretroviral therapy in Ghana.
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Occult Hepatitis B (OBH) in Clinical Settings. HEPATITIS MONTHLY 2012. [DOI: 10.5812/hapatmon.6126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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Alavian SM, Miri SM, Hollinger FB, Jazayeri SM. Occult Hepatitis B (OBH) in Clinical Settings. HEPATITIS MONTHLY 2012; 12:e6126. [PMID: 23087749 PMCID: PMC3475016 DOI: 10.5812/hepatmon.6126] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/20/2012] [Revised: 06/20/2012] [Accepted: 07/08/2012] [Indexed: 12/11/2022]
Abstract
CONTEXT Occult hepatitis B (OHB), or persistent HBV DNA in patients who are hepatitis B surface antigen (HBsAg) negative, is a recently recognized entity. In an attempt to summarize the issues, this review presents an overview of the current proposed hypothesis on the clinical relevance and also updates the knowledge on the classification of OHB in different clinical settings. EVIDENCE ACQUISITION OHB COULD BE FOUND IN DIFFERENT POPULATION AND CLINICAL BACKGROUNDS INCLUDING: viral co-infections (with either human immunodeficiency or hepatitis C viruses), HBV chronic carriers, dialysis patients, transplantation settings and certain clinical situations (named in here: special clinical settings) with no apparent distinguishable clinical parameters. RESULTS The exact magnitude, pathogenesis, and clinical relevance of OHB are unclear. Even the possible role exerted by this cryptic infection on liver disease outcome, and hepatocellular carcinoma development remains unknown. CONCLUSIONS Monitoring of Individuals with positive anti-HBc, mass immunization programs and improvement in diagnostic tools seem to be important to control the probability of transmission of HBV through cryptic HBV infection.
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Affiliation(s)
- Seyed Moayed Alavian
- Baqiyatallah Research Center for Gastroenterology and Liver Disease, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
| | - Seyed Mohammad Miri
- Baqiyatallah Research Center for Gastroenterology and Liver Disease, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
| | | | - Seyed Mohammad Jazayeri
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran
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Firnhaber C, Chen CY, Evans D, Maskew M, Schulz D, Reyneke A, Kramvis A. 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. Int J Infect Dis 2012; 16:e268-72. [DOI: 10.1016/j.ijid.2011.12.007] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2011] [Revised: 09/20/2011] [Accepted: 12/05/2011] [Indexed: 01/05/2023] Open
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Bagaglio S, Bianchi G, Danise A, Porrino L, Uberti-Foppa C, Lazzarin A, Castagna A, Morsica G. Longitudinal evaluation of occult hepatitis B infection in HIV-1 infected individuals during highly active antiretroviral treatment interruption and after HAART resumption. Infection 2011; 39:121-6. [PMID: 21424854 DOI: 10.1007/s15010-011-0093-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2010] [Accepted: 02/28/2011] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND OBJECTIVE The prevalence and clinical significance of overt hepatitis B (OHB) in human immunodeficiency virus (HIV)-infected individuals and the effect of HAART on this cryptic infection remain controversial. We have investigated the potential effect of the interruption and subsequent re-introduction of highly active antiretroviral therapy (HAART) on the frequency and dynamics of OHB in HIV-infected individuals. STUDY DESIGN This pilot study involved 29 HIV-infected individuals who tested positive for HB anti-core antibodies in the absence of surface antigen during a 100-week period (48-week-long interruption of HAART or lamivudine monotherapy plus 52 weeks of follow-up prior to HAART resumption). The frequency and dynamics of OHB were assessed by means of qualitative detection tests and quantification in the plasma. Resistance to HBV was determined by direct sequence analysis of the polymerase gene. RESULTS Of the 29 HIV-infected individuals enrolled in the study, nine (31%) showed signs of OHB during the 100-week study period: three patients showed intermittent HB virus (HBV)-DNAemia, while six patients were HBV-DNA positive only at 16 weeks following HAART resumption. The HBV-DNA load invariably fell below the sensitivity of the quantitative test (10(3 )copies/mL). The HIV-related immuno-virologic profile and biochemical parameters, including hepatic transaminases, of patients with at least one HBV-DNA positive test result were not significant different from those of individuals who consistently tested negative for HBV-DNA. The only significant parameter was a lower median change (Δ1) in the CD4+/CD8+ ratio (p = 0.038) in occult HBV cases compared to non-occult cases, between the HAART re-introduction time point and baseline. CONCLUSIONS The intermittent nature of HBV-DNAemia poses a diagnostic challenge, but no association was found with transaminase levels at any time.
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Affiliation(s)
- S Bagaglio
- Department of Infectious Diseases, San Raffaele Scientific Institute, via Stamira d'Ancona, 20, 20127, Milan, Italy
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N'Dri-Yoman T, Anglaret X, Messou E, Attia A, Polneau S, Toni T, Chenal H, Seyler C, Gabillard D, Wakasugi N, Eholié S, Danel C. Occult HBV infection in untreated HIV-infected adults in Côte d'Ivoire. Antivir Ther 2011; 15:1029-34. [PMID: 21041918 DOI: 10.3851/imp1641] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND In countries with high rates of chronic HBV, the World Health Organization recommends screening all HIV-infected adults for hepatitis B surface antigen (HBsAg) before initiating antiretroviral therapy (ART), and starting HIV-HBV-coinfected patients on regimens containing lamivudine (3TC) or emtricitabine (FTC) plus tenofovir disoproxil fumarate (TDF). Here, we estimated the prevalence of untreated HIV-infected adults with negative serum HBsAg and detectable plasma HBV DNA in Côte d'Ivoire. METHODS This was a cross-sectional survey. We tested all untreated HIV type-1 (HIV-1)-infected adults with CD4(+) T-cell counts <500 cells/mm(3) for HBsAg, hepatitis B core antibodies (anti-HBc) and HBsAg antibodies (anti-HBs). We measured plasma HBV DNA in patients who tested positive for HBsAg and/or anti-HBc. RESULTS We included 495 adults, of whom 73% were women. Median CD4(+) T-cell count was 329 cells/mm(3) and median HIV RNA was 4.9 log(10) copies/ml. Overall, 63 (13%) patients had chronic hepatitis B (HBsAg-positive), 115 (23%) had never been exposed to HBV (HBsAg-negative, anti-HBc-negative and anti-HBs-negative), 108 (22%) had signs of cured infection (anti-HBc-positive and anti-HBs-positive) and 209 (42%) had isolated anti-HBc (HBsAg-negative, anti-HBc-positive and anti-HBs-negative). Of these, 51 (10%) had detectable HBV DNA. Median HBV DNA level was 5.2 log(10) copies/ml (interquartile range [IQR] 3.2-8.8) for patients with chronic hepatitis and 2.2 log(10) copies/ml (IQR 1.8-2.7) for those with occult HBV infection. CONCLUSIONS Among ART-naive HIV-1-infected African adults, 13% were HBsAg-positive and 42% had isolated anti-HBc, including 10% who had occult HBV. The clinical implications of high occult HBV prevalence are unknown. Future studies should assess the benefits of routine use of 3TC or FTC plus TDF as first-line ART in African settings, where HBV DNA tests are unavailable.
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Reuter S, Oette M, Wilhelm FC, Beggel B, Kaiser R, Balduin M, Schweitzer F, Verheyen J, Adams O, Lengauer T, Fätkenheuer G, Pfister H, Häussinger D. Prevalence and characteristics of hepatitis B and C virus infections in treatment-naïve HIV-infected patients. Med Microbiol Immunol 2010; 200:39-49. [PMID: 20853118 DOI: 10.1007/s00430-010-0172-z] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2010] [Indexed: 02/07/2023]
Abstract
In HIV-infected treatment-naïve patients, we analyzed risk factors for either chronic hepatitis B (HBV) infection, occult HBV infection (OHBV) or a positive hepatitis C (HCV) serostatus. A total of 918 patients of the RESINA-cohort in Germany were included in this study. Before initiating antiretroviral therapy, clinical parameters were collected and blood samples were analyzed for antibodies against HIV, HBV and HCV, HBs antigen and viral nucleic acids for HIV and HBV. Present or past HBV infection (i.e. HBsAg and/or anti-HBc) was found in 43.4% of patients. HBsAg was detected in 4.5% (41/918) and HBV DNA in 6.1% (34/554), resulting in OHBV infection in 2.9% (16/554) of patients. OHBV infection could not be ruled out by the presence of anti-HBs (50.1%) or the absence of all HBV seromarkers (25%). A HCV-positive serostatus was associated with the IVDU transmission route, non-African ethnicity, elevated liver parameters (ASL or GGT) and low HIV viral load. Replicative HBV infection and HCV-positive serostatus both correlated with HIV resistance mutations (P = 0.001 and P = 0.028). HBV and HCV infection are frequent co-infections in HIV treatment-naive patients. These co-infections influence viral evolution, clinical parameters and serological markers. Consequently, HIV patients should routinely be tested for HBV and HCV infection before initiating HIV treatment. OHBV infection constituted almost half of all HBV infections with detectable HBV DNA. Due to a lack of risk factors indicating OHBV infection, HBV diagnosis should not only include serological markers but also the detection of HBV DNA.
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Affiliation(s)
- Stefan Reuter
- Clinic of Gastroenterology, Hepatology and Infectious Diseases, University Hospital, Moorenstr. 5, 40225 Duesseldorf, Germany.
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Brook G, Main J, Nelson M, Bhagani S, Wilkins E, Leen C, Fisher M, Gilleece Y, Gilson R, Freedman A, Kulasegaram R, Agarwal K, Sabin C, Deacon-Adams C. British HIV Association guidelines for the management of coinfection with HIV-1 and hepatitis B or C virus 2010. HIV Med 2010; 11:1-30. [PMID: 20059574 DOI: 10.1111/j.1468-1293.2009.00781.x] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- G Brook
- British HIV Association (BHIVA), BHIVA Secretariat, Mediscript Ltd, London, UK.
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Marque-Juillet S, Benghalia K, Monnier S, Fernand-Laurent C, Mazeron MC, Harzic M. Faut-il rechercher une hépatite B occulte chez les patients infectés par le virus de l’immunodéficience humaine (VIH) ? ACTA ACUST UNITED AC 2010; 58:e39-42. [DOI: 10.1016/j.patbio.2009.07.031] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2009] [Accepted: 07/19/2009] [Indexed: 02/07/2023]
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Bloquel B, Jeulin H, Burty C, Letranchant L, Rabaud C, Venard V. Occult hepatitis B infection in patients infected with HIV: report of two cases of hepatitis B reactivation and prevalence in a hospital cohort. J Med Virol 2010; 82:206-12. [PMID: 20029819 DOI: 10.1002/jmv.21685] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Patients co-infected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are particularly at risk of hepatitis B reactivation. Two cases of patients infected with HIV with isolated anti-HBc antibodies who had experienced an HBV reactivation are described. In the two cases HBV reactivation occurred after withdrawal of anti-retroviral treatment with anti-HBV activity from the patients' highly active antiretroviral therapy (HAART), in accordance with HIV genotypic resistance profiles. Consequently, plasma samples from 383 patients infected with HIV were tested to assess the prevalence of occult HBV infection in the Infectious Diseases Department Unit of Nancy Hospital by investigating serological patterns and HBV replication. Forty-five percent (172/383) of patients had had previous contact with HBV. Isolated anti-HBc antibodies were observed in 48 patients (48/383, 12%) and, among these, 2 were HBV-DNA positive. Since 75% (288/383) of the patients were treated with HAART, including at least one drug active against HBV, occult HBV infection was perhaps unrecognized. In cases of HIV infection, all patients should be screened for HBV infection and the knowledge of HBV status as well as the monitoring of HBV viral load are essential in preventing HBV reactivation. Consideration should be given to the continuation of drugs with anti-HBV activity in co-infected patients receiving HAART, as cessation of therapy is associated with a risk of HBV reactivation. At least, close monitoring of the HBV viral load is warranted in such situations.
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Affiliation(s)
- B Bloquel
- Laboratory of Virology, CHU Nancy Brabois, Vandoeuvre-lès-Nancy, France
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32
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Kozłowska J, Mikuła T, Staćczak W, Wiercićska-Drapało A. Hepatitis B prophylaxis in HIV-infected patients. HIV & AIDS REVIEW 2010. [DOI: 10.1016/s1730-1270(11)60002-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
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Compston LI, Li C, Sarkodie F, Owusu-Ofori S, Opare-Sem O, Allain JP. Prevalence of persistent and latent viruses in untreated patients infected with HIV-1 from Ghana, West Africa. J Med Virol 2009; 81:1860-8. [PMID: 19774687 DOI: 10.1002/jmv.21614] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Only limited epidemiological data, pertaining to the prevalence of common persistent viruses has been reported in Ghana. This study was conducted to determine the prevalence of persistent viruses in individuals with untreated HIV-1 infection and uninfected blood donors. Paired plasma and cellular samples from HIV-negative blood donors, asymptomatic HIV and symptomatic/AIDS cohorts were screened by multiplex PCR then qPCR for parvovirus B19 (B19V), hepatitis B virus (HBV), GB virus-C (GBV-C), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus-8 (HHV-8) and varicella-zoster virus (VZV). IgG antibodies specific to each target virus were tested to determine exposure rates. No evidence of viraemia was found for B19V and VZV in any group. Prevalence of GBV-C plasma viraemia was significantly higher in asymptomatic and symptomatic HIV infection (16.7%) and (16.2%) than in blood donors (4%) P < 0.005. Occult HBV infection was significantly more frequent in symptomatic HIV infection (10.9%) compared to asymptomatic HIV (3.6%) and blood donors (1.6%) P < 0.005. Although there was a high background of EBV viraemia in cellular fractions of blood donors (8.3%), it was significantly higher in asymptomatic (44.6%) and symptomatic HIV (14.6%) P < 0.0001. For CMV, the significantly increased prevalence of viraemia was only observed in the plasma fraction of the symptomatic HIV-1/AIDS patients (7.6%) compared to asymptomatic individuals (1.8%) and blood donors (0.8%) P < or = 0.001. The background seroprevalence in blood donors was high for B19V (> or =64%), HBV (> or =70%), CMV and EBV (> or =90%) and was significantly increased in HIV infections for HBV, CMV, VZV (symptomatic HIV), and HHV-8 (asymptomatic and symptomatic HIV).
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Affiliation(s)
- Lara Isobel Compston
- Department of Haematology, Division of Transfusion Medicine, University of Cambridge, Cambridge Blood Centre, Cambridge CB2 2PT, United Kingdom
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Morsica G, Ancarani F, Bagaglio S, Maracci M, Cicconi P, Cozzi Lepri A, Antonucci G, Bruno R, Santantonio T, Tacconi L, Baldelli F, Piscopo R, Santoro D, Lazzarin A, D'Arminio Monforte A. Occult hepatitis B virus infection in a cohort of HIV-positive patients: correlation with hepatitis C virus coinfection, virological and immunological features. Infection 2009; 37:445-9. [PMID: 19669092 DOI: 10.1007/s15010-008-8194-9] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2008] [Accepted: 10/28/2008] [Indexed: 12/16/2022]
Abstract
BACKGROUND An evaluation of the prevalence of occult hepatitis B virus (HBV) infection in HIV-positive individuals is important as HBV infection may have an impact on the outcome of the liver disease in these patients. MATERIALS AND METHODS Of the 1,593 HIV-positive subjects enrolled in the Italian Cohort Naïve Antiretroviral (ICONA) program, 175 (10.9%) were selected for inclusion in the study on the basis of hepatitis B surface antigen (HBsAg) negativity and antibody to hepatitis B core antigen (anti- HBc) positivity; 101/175 (58%) were also anti-hepatitis C virus (HCV) positive. HBV-DNA was detected in plasma using a highly sensitive PCR assay (detection limit: 2.6 copies/ml). Two different genomic regions were assayed. Quantification was performed by real-time PCR. The HBV genotype was determined in 20 cases with occult HBV infection. Data on the antiretroviral therapy (ART) regimen was obtained in 169 individuals: 53 (31.4%) patients were ART-naive, 46 (27.2%) were under ART without lamivudine or tenofovir, and the remaining 70 (41.4%) were under ART including lamivudine or tenofovir. RESULTS 27/175 (15%) patients had detectable HBV-DNA in their plasma: 21/101 (21%) were anti-HCV positive and 6/74 (8%) were anti-HCV negative. Genotype D was invariably found in the 20 cases analyzed. Occult HBV infection was significantly higher in HCV-coinfected subjects: adjusted OR 5.02, 95% CI 1.31-19.26, p = 0.02. The value was not associated with immune status, HIV load, or ART regimen. CONCLUSIONS In relation to the high prevalence of occult HBV infection, particularly in HIV/HCV-coinfected individuals, it is necessary to clarify the clinical impact of this cryptic infection by monitoring HBV-DNA in plasma using the correct approach. Similarly to HBsAg-positive individuals of the Mediterranean area, HBV genotype D is invariably detected in this cohort of HIV-infected patients with occult HBV infection.
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Affiliation(s)
- G Morsica
- Dept. of Infectious Diseases, S. Raffaele Scientific Institute, Milan, Italy.
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Geretti AM, Brook G, Cameron C, Chadwick D, Heyderman RS, MacMahon E, Pozniak A, Ramsay M, Schuhwerk M. British HIV Association guidelines for immunization of HIV-infected adults 2008. HIV Med 2009; 9:795-848. [PMID: 18983477 DOI: 10.1111/j.1468-1293.2008.00637.x] [Citation(s) in RCA: 88] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- A M Geretti
- Department of Virology, Royal Free Hospital, Royal Free and University College Medical School, Pond Street, London NW3 2QG, UK.
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Miyagawa M, Minami M, Fujii K, Sendo R, Mori K, Shimizu D, Nakajima T, Yasui K, Itoh Y, Taniwaki M, Okanoue T, Yoshikawa T. Molecular characterization of a variant virus that caused de novo hepatitis B without elevation of hepatitis B surface antigen after chemotherapy with rituximab. J Med Virol 2008; 80:2069-78. [PMID: 19040281 DOI: 10.1002/jmv.21311] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-negative patients following treatment with rituximab has been reported increasingly. The aim of this study was to investigate the molecular mechanisms underlying HBV reactivation in an HBsAg-negative patient. HBV was reactivated in a 75-year-old man following chemotherapy with rituximab, without elevation of HBsAg. The patient's full-length HBV genome was cloned and the entire sequence was determined. Transfection studies were performed in vitro using recombinant wild-type HBV (wild-type), the patient's HBV (patient), and two chimeric HBV constructs, in which the preS/S region of the patient and wild-type virus had been exchanged with one another. Secreted HBsAg and intra- and extra-cellular HBV DNA were measured. The number of amino acid substitutions in HBV from this patient was much higher than in previous reports of HBV mutants, such as occult HBV and vaccine escape HBV mutants. Levels of HBsAg and HBV DNA production in vitro were significantly lower in the patient compared to wild-type transfections. From analyses of the chimeric constructs, the altered preS/S region was responsible mainly for this impairment. These results show that highly mutated HBV can reactivate after chemotherapy with rituximab, despite an unusually large number of mutations, resulting in impaired viral replication in vitro. Severe immune suppression, probably caused by rituximab, may permit reactivation of highly mutated HBV. These findings have important clinical implications for the prevention and management of HBV reactivation and may explain partially the mechanism of recent, unusual cases of HBV reactivation.
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Affiliation(s)
- Masami Miyagawa
- Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
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Araujo NM, Branco-Vieira M, Silva ACM, Pilotto JH, Grinsztejn B, de Almeida AJ, Trepo C, Gomes SA. Occult hepatitis B virus infection in HIV-infected patients: Evaluation of biochemical, virological and molecular parameters. Hepatol Res 2008; 38:1194-203. [PMID: 18624719 DOI: 10.1111/j.1872-034x.2008.00392.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
AIM To determine the prevalence of occult hepatitis B virus (HBV) infection in a group of human immunodeficiency virus (HIV)-infected Brazilian patients and to investigate its association with biochemical, virological and molecular features. METHODS Sera from 43 patients positive for HBV core antibody and negative for HBV surface antigen (HBsAg) were tested for HBV DNA positivity by semi-nested PCR. HBV loads were assessed by real-time PCR. S gene was cloned and sequenced for HBV isolates from 3 patients. HBsAg expression of these cases was performed in HuH7 cells. RESULTS HBV DNA was found in 6/43 (14%) samples, all except one associated with low viral loads. Occult HBV infection was further correlated with anti-hepatitis C virus (anti-HCV) antibodies positivity, but not with alanine aminotransferase (ALT) elevated levels. S gene sequences derived from three patients were determined. Two of them displayed mutations that may explain HBsAg negativity. In the first one, a stop codon mutation was found at position 216 in the C-terminal end of HBsAg. In the second patient, E164D and I195M substitutions in HBsAg, associated with lamivudine-resistance mutations in the polymerase were identified. As expected, all clones showing those mutations displayed undetectable or very low levels of HBsAg. CONCLUSION Occult HBV infection was frequent in HIV-infected patients, was not associated with ALT elevation but significantly correlated with HCV seropositivity. The low viremia and the detection of HBsAg mutants confirm that multifactorial mechanisms are involved in occult HBV infection. HBV molecular monitoring should be employed for an adequate management of HBV/HIV co-infected patients.
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Affiliation(s)
- Natalia M Araujo
- Laboratory of Molecular Virology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ, Brazil
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