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Published in: Virology Journal 1/2014

Open Access 01-12-2014 | Case Report

Spontaneous reactivation of hepatitis B virus replication in an HIV coinfected patient with isolated anti-Hepatitis B core antibodies

Authors: Rongjuan Pei, Sebastian Grund, Jens Verheyen, Stefan Esser, Xinwen Chen, Mengji Lu

Published in: Virology Journal | Issue 1/2014

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Abstract

Co-infections with HBV (hepatitis B virus) occur in HIV (human immunodeficiency virus) patients frequently. It has been reported that an effective treatment of HIV can also lead to a suppression of HBV and to anti-HBs seroconversion in HBV-infected patients. Here, we report a spontaneous reactivation of HBV replication in an HIV-infected patient with anti-HBc as the only marker of chronic HBV infection. The patient was known to be coinfected with HIV and HBV for years and the HBV DNA was measured repeatedly at low levels. A significant increase of HBV DNA up to 1.7x107 IU/ml was found accompanied with clinical symptoms of hepatitis. Multiple mutations occurred in the S gene during the flare-up of HBV as shown by sequencing, including I103T, K122R, M133I, F134V, D144E, V164E and L175S. Anti-HIV/HBV treatment led to a resolution of symptoms and to a decrease in the HIV RNA and HBV DNA viral load. It is possible that the accumulated mutations during HBV replication were selected and responsible for the reactivation.
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Literature
1.
2.
go back to reference Bodsworth NJ, Cooper DA, Donovan B: The influence of human immunodeficiency virus type 1 infection on the development of the hepatitis B virus carrier state. J Infect Dis 1991, 163: 1138-1140. 10.1093/infdis/163.5.1138PubMedCrossRef Bodsworth NJ, Cooper DA, Donovan B: The influence of human immunodeficiency virus type 1 infection on the development of the hepatitis B virus carrier state. J Infect Dis 1991, 163: 1138-1140. 10.1093/infdis/163.5.1138PubMedCrossRef
3.
go back to reference Vento S, Di Perri G, Garofano T, Concia E, Bassetti D: Reactivation of hepatitis B in AIDS. Lancet 1989, 2: 108-109.PubMedCrossRef Vento S, Di Perri G, Garofano T, Concia E, Bassetti D: Reactivation of hepatitis B in AIDS. Lancet 1989, 2: 108-109.PubMedCrossRef
4.
5.
go back to reference Yeo W, Chan PK, Zhong S, Ho WM, Steinberg JL, Tam JS, Hui P, Leung NW, Zee B, Johnson PJ: Frequency of hepatitis B virus reactivation in cancer patients undergoing cytotoxic chemotherapy: a prospective study of 626 patients with identification of risk factors. J Med Virol 2000, 62: 299-307. 10.1002/1096-9071(200011)62:3<299::AID-JMV1>3.0.CO;2-0PubMedCrossRef Yeo W, Chan PK, Zhong S, Ho WM, Steinberg JL, Tam JS, Hui P, Leung NW, Zee B, Johnson PJ: Frequency of hepatitis B virus reactivation in cancer patients undergoing cytotoxic chemotherapy: a prospective study of 626 patients with identification of risk factors. J Med Virol 2000, 62: 299-307. 10.1002/1096-9071(200011)62:3<299::AID-JMV1>3.0.CO;2-0PubMedCrossRef
6.
go back to reference Esteve M, Saro C, Gonzalez-Huix F, Suarez F, Forne M, Viver JM: Chronic hepatitis B reactivation following infliximab therapy in Crohn’s disease patients: need for primary prophylaxis. Gut 2004, 53: 1363-1365. 10.1136/gut.2004.040675PubMedPubMedCentralCrossRef Esteve M, Saro C, Gonzalez-Huix F, Suarez F, Forne M, Viver JM: Chronic hepatitis B reactivation following infliximab therapy in Crohn’s disease patients: need for primary prophylaxis. Gut 2004, 53: 1363-1365. 10.1136/gut.2004.040675PubMedPubMedCentralCrossRef
7.
go back to reference Marcellin P, Giostra E, Martinot-Peignoux M, Loriot MA, Jaegle ML, Wolf P, Degott C, Degos F, Benhamou JP: Redevelopment of hepatitis B surface antigen after renal transplantation. Gastroenterology 1991, 100: 1432-1434.PubMed Marcellin P, Giostra E, Martinot-Peignoux M, Loriot MA, Jaegle ML, Wolf P, Degott C, Degos F, Benhamou JP: Redevelopment of hepatitis B surface antigen after renal transplantation. Gastroenterology 1991, 100: 1432-1434.PubMed
8.
go back to reference Hui CK, Cheung WW, Au WY, Lie AK, Zhang HY, Yueng YH, Wong BC, Leung N, Kwong YL, Liang R, Lau GK: Hepatitis B reactivation after withdrawal of pre-emptive lamivudine in patients with haematological malignancy on completion of cytotoxic chemotherapy. Gut 2005, 54: 1597-1603. 10.1136/gut.2005.070763PubMedPubMedCentralCrossRef Hui CK, Cheung WW, Au WY, Lie AK, Zhang HY, Yueng YH, Wong BC, Leung N, Kwong YL, Liang R, Lau GK: Hepatitis B reactivation after withdrawal of pre-emptive lamivudine in patients with haematological malignancy on completion of cytotoxic chemotherapy. Gut 2005, 54: 1597-1603. 10.1136/gut.2005.070763PubMedPubMedCentralCrossRef
9.
go back to reference Laskus T, Rakela J, Tong MJ, Persing DH: Nucleotide sequence analysis of the precore region in patients with spontaneous reactivation of chronic hepatitis B. Dig Dis Sci 1994, 39: 2000-2006. 10.1007/BF02088138PubMedCrossRef Laskus T, Rakela J, Tong MJ, Persing DH: Nucleotide sequence analysis of the precore region in patients with spontaneous reactivation of chronic hepatitis B. Dig Dis Sci 1994, 39: 2000-2006. 10.1007/BF02088138PubMedCrossRef
10.
go back to reference Altfeld M, Rockstroh JK, Addo M, Kupfer B, Pult I, Will H, Spengler U: Reactivation of hepatitis B in a long-term anti-HBs-positive patient with AIDS following lamivudine withdrawal. J Hepatol 1998, 29: 306-309. 10.1016/S0168-8278(98)80017-2PubMedCrossRef Altfeld M, Rockstroh JK, Addo M, Kupfer B, Pult I, Will H, Spengler U: Reactivation of hepatitis B in a long-term anti-HBs-positive patient with AIDS following lamivudine withdrawal. J Hepatol 1998, 29: 306-309. 10.1016/S0168-8278(98)80017-2PubMedCrossRef
11.
go back to reference Neau D, Schvoerer E, Robert D, Dubois F, Dutronc H, Fleury HJ, Ragnaud JM: Hepatitis B exacerbation with a precore mutant virus following withdrawal of lamivudine in a human immunodeficiency virus-infected patient. J Infect 2000, 41: 192-194. 10.1053/jinf.2000.0724PubMedCrossRef Neau D, Schvoerer E, Robert D, Dubois F, Dutronc H, Fleury HJ, Ragnaud JM: Hepatitis B exacerbation with a precore mutant virus following withdrawal of lamivudine in a human immunodeficiency virus-infected patient. J Infect 2000, 41: 192-194. 10.1053/jinf.2000.0724PubMedCrossRef
12.
go back to reference Martel N, Cotte L, Trabaud MA, Trepo C, Zoulim F, Gomes SA, Kay A: Probable corticosteroid-induced reactivation of latent hepatitis B virus infection in an HIV-positive patient involving immune escape. J Infect Dis 2012, 205: 1757-1761. 10.1093/infdis/jis268PubMedCrossRef Martel N, Cotte L, Trabaud MA, Trepo C, Zoulim F, Gomes SA, Kay A: Probable corticosteroid-induced reactivation of latent hepatitis B virus infection in an HIV-positive patient involving immune escape. J Infect Dis 2012, 205: 1757-1761. 10.1093/infdis/jis268PubMedCrossRef
13.
go back to reference Costantini A, Marinelli K, Biagioni G, Monachetti A, Ferreri ML, Butini L, Montroni M, Manzin A, Bagnarelli P: Molecular analysis of hepatitis B virus (HBV) in an HIV co-infected patient with reactivation of occult HBV infection following discontinuation of lamivudine-including antiretroviral therapy. BMC Infect Dis 2011, 11: 310. 10.1186/1471-2334-11-310PubMedPubMedCentralCrossRef Costantini A, Marinelli K, Biagioni G, Monachetti A, Ferreri ML, Butini L, Montroni M, Manzin A, Bagnarelli P: Molecular analysis of hepatitis B virus (HBV) in an HIV co-infected patient with reactivation of occult HBV infection following discontinuation of lamivudine-including antiretroviral therapy. BMC Infect Dis 2011, 11: 310. 10.1186/1471-2334-11-310PubMedPubMedCentralCrossRef
14.
go back to reference Henke-Gendo C, Amini-Bavil-Olyaee S, Challapalli D, Trautwein C, Deppe H, Schulz TF, Heim A, Tacke F: Symptomatic hepatitis B virus (HBV) reactivation despite reduced viral fitness is associated with HBV test and immune escape mutations in an HIV-coinfected patient. J Infect Dis 2008, 198: 1620-1624. 10.1086/592987PubMedCrossRef Henke-Gendo C, Amini-Bavil-Olyaee S, Challapalli D, Trautwein C, Deppe H, Schulz TF, Heim A, Tacke F: Symptomatic hepatitis B virus (HBV) reactivation despite reduced viral fitness is associated with HBV test and immune escape mutations in an HIV-coinfected patient. J Infect Dis 2008, 198: 1620-1624. 10.1086/592987PubMedCrossRef
15.
go back to reference Grob P, Jilg W, Bornhak H, Gerken G, Gerlich W, Gunther S, Hess G, Hudig H, Kitchen A, Margolis H, et al.: Serological pattern “anti-HBc alone”: report on a workshop. J Med Virol 2000, 62: 450-455. 10.1002/1096-9071(200012)62:4<450::AID-JMV9>3.0.CO;2-YPubMedCrossRef Grob P, Jilg W, Bornhak H, Gerken G, Gerlich W, Gunther S, Hess G, Hudig H, Kitchen A, Margolis H, et al.: Serological pattern “anti-HBc alone”: report on a workshop. J Med Virol 2000, 62: 450-455. 10.1002/1096-9071(200012)62:4<450::AID-JMV9>3.0.CO;2-YPubMedCrossRef
16.
go back to reference Alhababi F, Sallam TA, Tong CY: The significance of ‘anti-HBc only’ in the clinical virology laboratory. J Clin Virol 2003, 27: 162-169. 10.1016/S1386-6532(02)00171-3PubMedCrossRef Alhababi F, Sallam TA, Tong CY: The significance of ‘anti-HBc only’ in the clinical virology laboratory. J Clin Virol 2003, 27: 162-169. 10.1016/S1386-6532(02)00171-3PubMedCrossRef
17.
go back to reference Ponde RA, Cardoso DD, Ferro MO: The underlying mechanisms for the ‘anti-HBc alone’ serological profile. Arch Virol 2010, 155: 149-158. 10.1007/s00705-009-0559-6PubMedCrossRef Ponde RA, Cardoso DD, Ferro MO: The underlying mechanisms for the ‘anti-HBc alone’ serological profile. Arch Virol 2010, 155: 149-158. 10.1007/s00705-009-0559-6PubMedCrossRef
18.
go back to reference Perez-Rodriguez MT, Sopena B, Crespo M, Rivera A, Gonzalez Del Blanco T, Ocampo A, Martinez-Vazquez C: Clinical significance of “anti-HBc alone” in human immunodeficiency virus-positive patients. World J Gastroenterol 2009, 15: 1237-1241. 10.3748/wjg.15.1237PubMedPubMedCentralCrossRef Perez-Rodriguez MT, Sopena B, Crespo M, Rivera A, Gonzalez Del Blanco T, Ocampo A, Martinez-Vazquez C: Clinical significance of “anti-HBc alone” in human immunodeficiency virus-positive patients. World J Gastroenterol 2009, 15: 1237-1241. 10.3748/wjg.15.1237PubMedPubMedCentralCrossRef
19.
go back to reference Berger A, Doerr HW, Rabenau HF, Weber B: High frequency of HCV infection in individuals with isolated antibody to hepatitis B core antigen. Intervirology 2000, 43: 71-76. 10.1159/000025026PubMedCrossRef Berger A, Doerr HW, Rabenau HF, Weber B: High frequency of HCV infection in individuals with isolated antibody to hepatitis B core antigen. Intervirology 2000, 43: 71-76. 10.1159/000025026PubMedCrossRef
20.
go back to reference Knoll A, Hartmann A, Hamoshi H, Weislmaier K, Jilg W: Serological pattern “anti-HBc alone”: characterization of 552 individuals and clinical significance. World J Gastroenterol 2006, 12: 1255-1260.PubMedPubMedCentral Knoll A, Hartmann A, Hamoshi H, Weislmaier K, Jilg W: Serological pattern “anti-HBc alone”: characterization of 552 individuals and clinical significance. World J Gastroenterol 2006, 12: 1255-1260.PubMedPubMedCentral
21.
go back to reference Gandhi RT, Wurcel A, Lee H, McGovern B, Boczanowski M, Gerwin R, Corcoran CP, Szczepiorkowski Z, Toner S, Cohen DE, et al.: Isolated antibody to hepatitis B core antigen in human immunodeficiency virus type-1-infected individuals. Clin Infect Dis 2003, 36: 1602-1605. 10.1086/375084PubMedCrossRef Gandhi RT, Wurcel A, Lee H, McGovern B, Boczanowski M, Gerwin R, Corcoran CP, Szczepiorkowski Z, Toner S, Cohen DE, et al.: Isolated antibody to hepatitis B core antigen in human immunodeficiency virus type-1-infected individuals. Clin Infect Dis 2003, 36: 1602-1605. 10.1086/375084PubMedCrossRef
22.
go back to reference Chamorro AJ, Casado JL, Bellido D, Moreno S: Reactivation of hepatitis B in an HIV-infected patient with antibodies against hepatitis B core antigen as the only serological marker. Eur J Clin Microbiol Infect Dis 2005, 24: 492-494. 10.1007/s10096-005-1355-1PubMedCrossRef Chamorro AJ, Casado JL, Bellido D, Moreno S: Reactivation of hepatitis B in an HIV-infected patient with antibodies against hepatitis B core antigen as the only serological marker. Eur J Clin Microbiol Infect Dis 2005, 24: 492-494. 10.1007/s10096-005-1355-1PubMedCrossRef
23.
go back to reference Kreutz C: Molecular, immunological and clinical properties of mutated hepatitis B viruses. J Cell Mol Med 2002, 6: 113-143. 10.1111/j.1582-4934.2002.tb00317.xPubMedCrossRef Kreutz C: Molecular, immunological and clinical properties of mutated hepatitis B viruses. J Cell Mol Med 2002, 6: 113-143. 10.1111/j.1582-4934.2002.tb00317.xPubMedCrossRef
24.
go back to reference Oon CJ, Lim GK, Ye Z, Goh KT, Tan KL, Yo SL, Hopes E, Harrison TJ, Zuckerman AJ: Molecular epidemiology of hepatitis B virus vaccine variants in Singapore. Vaccine 1995, 13: 699-702. 10.1016/0264-410X(94)00080-7PubMedCrossRef Oon CJ, Lim GK, Ye Z, Goh KT, Tan KL, Yo SL, Hopes E, Harrison TJ, Zuckerman AJ: Molecular epidemiology of hepatitis B virus vaccine variants in Singapore. Vaccine 1995, 13: 699-702. 10.1016/0264-410X(94)00080-7PubMedCrossRef
25.
go back to reference Kim KH, Lee KH, Chang HY, Ahn SH, Tong S, Yoon YJ, Seong BL, Kim SI, Han KH: Evolution of hepatitis B virus sequence from a liver transplant recipient with rapid breakthrough despite hepatitis B immune globulin prophylaxis and lamivudine therapy. J Med Virol 2003, 71: 367-375. 10.1002/jmv.10503PubMedCrossRef Kim KH, Lee KH, Chang HY, Ahn SH, Tong S, Yoon YJ, Seong BL, Kim SI, Han KH: Evolution of hepatitis B virus sequence from a liver transplant recipient with rapid breakthrough despite hepatitis B immune globulin prophylaxis and lamivudine therapy. J Med Virol 2003, 71: 367-375. 10.1002/jmv.10503PubMedCrossRef
26.
go back to reference Carman WF, Zanetti AR, Karayiannis P, Waters J, Manzillo G, Tanzi E, Zuckerman AJ, Thomas HC: Vaccine-induced escape mutant of hepatitis B virus. Lancet 1990, 336: 325-329. 10.1016/0140-6736(90)91874-APubMedCrossRef Carman WF, Zanetti AR, Karayiannis P, Waters J, Manzillo G, Tanzi E, Zuckerman AJ, Thomas HC: Vaccine-induced escape mutant of hepatitis B virus. Lancet 1990, 336: 325-329. 10.1016/0140-6736(90)91874-APubMedCrossRef
27.
go back to reference Zhang JM, Xu Y, Wang XY, Yin YK, Wu XH, Weng XH, Lu M: Coexistence of hepatitis B surface antigen (HBsAg) and heterologous subtype-specific antibodies to HBsAg among patients with chronic hepatitis B virus infection. Clin Infect Dis 2007, 44: 1161-1169. 10.1086/513200PubMedCrossRef Zhang JM, Xu Y, Wang XY, Yin YK, Wu XH, Weng XH, Lu M: Coexistence of hepatitis B surface antigen (HBsAg) and heterologous subtype-specific antibodies to HBsAg among patients with chronic hepatitis B virus infection. Clin Infect Dis 2007, 44: 1161-1169. 10.1086/513200PubMedCrossRef
28.
go back to reference Weinberger KM, Bauer T, Bohm S, Jilg W: High genetic variability of the group-specific a-determinant of hepatitis B virus surface antigen (HBsAg) and the corresponding fragment of the viral polymerase in chronic virus carriers lacking detectable HBsAg in serum. J Gen Virol 2000, 81: 1165-1174.PubMedCrossRef Weinberger KM, Bauer T, Bohm S, Jilg W: High genetic variability of the group-specific a-determinant of hepatitis B virus surface antigen (HBsAg) and the corresponding fragment of the viral polymerase in chronic virus carriers lacking detectable HBsAg in serum. J Gen Virol 2000, 81: 1165-1174.PubMedCrossRef
29.
go back to reference Gupta S, Govindarajan S, Fong TL, Redeker AG: Spontaneous reactivation in chronic hepatitis B: patterns and natural history. J Clin Gastroenterol 1990, 12: 562-568. 10.1097/00004836-199010000-00015PubMedCrossRef Gupta S, Govindarajan S, Fong TL, Redeker AG: Spontaneous reactivation in chronic hepatitis B: patterns and natural history. J Clin Gastroenterol 1990, 12: 562-568. 10.1097/00004836-199010000-00015PubMedCrossRef
30.
go back to reference Brunetto MR, Cerenzia MT, Oliveri F, Piantino P, Randone A, Calvo PL, Manzini P, Rocca G, Galli C, Bonino F: Monitoring the natural course and response to therapy of chronic hepatitis B with an automated semi-quantitative assay for IgM anti-HBc. J Hepatol 1993, 19: 431-436. 10.1016/S0168-8278(05)80554-9PubMedCrossRef Brunetto MR, Cerenzia MT, Oliveri F, Piantino P, Randone A, Calvo PL, Manzini P, Rocca G, Galli C, Bonino F: Monitoring the natural course and response to therapy of chronic hepatitis B with an automated semi-quantitative assay for IgM anti-HBc. J Hepatol 1993, 19: 431-436. 10.1016/S0168-8278(05)80554-9PubMedCrossRef
31.
go back to reference Chou CH, Chen PJ, Lee PH, Cheng AL, Hsu HC, Cheng JC: Radiation-induced hepatitis B virus reactivation in liver mediated by the bystander effect from irradiated endothelial cells. Clin Cancer Res 2007, 13: 851-857. 10.1158/1078-0432.CCR-06-2459PubMedCrossRef Chou CH, Chen PJ, Lee PH, Cheng AL, Hsu HC, Cheng JC: Radiation-induced hepatitis B virus reactivation in liver mediated by the bystander effect from irradiated endothelial cells. Clin Cancer Res 2007, 13: 851-857. 10.1158/1078-0432.CCR-06-2459PubMedCrossRef
32.
go back to reference Wijaya I, Hasan I: Reactivation of hepatitis B virus associated with chemotherapy and immunosuppressive agent. Acta Med Indones 2013, 45: 61-66.PubMed Wijaya I, Hasan I: Reactivation of hepatitis B virus associated with chemotherapy and immunosuppressive agent. Acta Med Indones 2013, 45: 61-66.PubMed
33.
go back to reference Chou CH, Chen PJ, Jeng YM, Cheng AL, Huang LR, Cheng JC: Synergistic effect of radiation and interleukin-6 on hepatitis B virus reactivation in liver through STAT3 signaling pathway. Int J Radiat Oncol Biol Phys 2009, 75: 1545-1552. 10.1016/j.ijrobp.2008.12.072PubMedCrossRef Chou CH, Chen PJ, Jeng YM, Cheng AL, Huang LR, Cheng JC: Synergistic effect of radiation and interleukin-6 on hepatitis B virus reactivation in liver through STAT3 signaling pathway. Int J Radiat Oncol Biol Phys 2009, 75: 1545-1552. 10.1016/j.ijrobp.2008.12.072PubMedCrossRef
Metadata
Title
Spontaneous reactivation of hepatitis B virus replication in an HIV coinfected patient with isolated anti-Hepatitis B core antibodies
Authors
Rongjuan Pei
Sebastian Grund
Jens Verheyen
Stefan Esser
Xinwen Chen
Mengji Lu
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2014
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/1743-422X-11-9

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