Management of HBV/HIV-Coinfected Patients

Norah J. Shire; Kenneth E. Sherman

doi:10.1055/s-2005-915646

Seminars in Liver Disease, Table of Contents

Semin Liver Dis 2005; 25: 48-57
DOI: 10.1055/s-2005-915646

Management of HBV/HIV-Coinfected Patients

Norah J. Shire¹ ^, ³ , Kenneth E. Sherman² ^, ³

¹Epidemiologist, University of Cincinnati, Cincinnati, Ohio
²Chair, University of Cincinnati, Cincinnati, Ohio
³Division of Digestive Diseases, University of Cincinnati, Cincinnati, Ohio

Abstract

ABSTRACT

Coinfection with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) is common as a result of shared routes of transmission, especially in high-risk groups such as injection drug users and persons with hemophilia. HIV is known to influence the natural history of HBV, hastening progression to end-stage liver disease and cirrhosis. Antiretroviral therapy for HIV, and associated immune reconstitution, may result in immune-mediated liver damage as HBV-infected hepatocytes are targeted. This can lead to liver enzyme elevations that may be misattributed to drug-related toxicity. Thus, it is important that HIV-infected patients be tested for HBV and that clinicians be aware of the possibility of atypical serologic markers of HBV in HIV-infected patients. In managing coinfected patients, control of HIV is the priority. In patients with controlled HIV who are candidates for HBV therapy, the goals are the same as in the HBV-monoinfected population: hepatitis B e antigen seroconversion, liver enzyme normalization, and HBV DNA suppression. Treatment options include interferon-based regimens, lamivudine, adefovir, tenofovir, and entecavir. All of these agents have been shown to be relatively effective in HBV-monoinfected patients. However, few randomized, controlled HBV treatment trials have been conducted in coinfected subjects, and thus additional studies are warranted.

KEYWORDS

HBV - HIV - coinfection - hepatitis

Full Text

References

REFERENCES

1 Tsukuma H, Hiyama T, Tanaka S et al.. Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med. 1993; 328 1797-1801
2 Shi J, Zhu L, Liu S, Xie W F. A meta-analysis of case-control studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma in China. Br J Cancer. 2005; 92 607-612
3 Parkin D M, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000. Int J Cancer. 2001; 94 153-156
4 World Health Organization (WHO) Fact Sheet WHO/204. Hepatitis B .2000 http://Available at: www.who.int/mediacentre/factsheets/fs204/en Accessed May 11, 2005
5 Law W P, Duncombe C J, Mahanontharit A et al.. Impact of viral hepatitis co-infection on response to antiretroviral therapy and HIV disease progression in the HIV-NAT cohort. AIDS. 2004; 18 1169-1177
6 Konopnicki D, Mocroft A, de Wit S et al.. Hepatitis B and HIV: prevalence, AIDS progression, response to highly active antiretroviral therapy and increased mortality in the EuroSIDA cohort. AIDS. 2005; 19 593-601
7 Bonacini M, Louie S, Bzowej N, Wohl A R. Survival in patients with HIV infection and viral hepatitis B or C: a cohort study. AIDS. 2004; 18 2039-2045
8 Thio C L, Seaberg E C, Skolasky Jr R et al.. HIV-1, hepatitis B virus, and risk of liver-related mortality in the Multicenter Cohort Study (MACS). Lancet. 2002; 360 1921-1926
9 MacKellar D A, Valleroy L A, Secura G M et al.. Two decades after vaccine license: hepatitis B immunization and infection among young men who have sex with men. Am J Public Health. 2001; 91 965-971
10 Rogers A S, Lindsey J C, Futterman D C, Zimmer B, Abdalian S E, D'Angelo L J. for the Pediatric AIDS Clinical Trials Group Protocol 220 Team . Serologic examination of hepatitis B infection and immunization in HIV-positive youth and associated risks. AIDS Patient Care STDS. 2000; 14 651-657
11 Kuo I, Sherman S G, Thomas D L, Strathdee S A. Hepatitis B virus infection and vaccination among young injection and non-injection drug users: missed opportunities to prevent infection. Drug Alcohol Depend. 2004; 73 69-78
12 Coleman P J, McQuillan G M, Moyer L A, Lambert S B, Margolis H S. Incidence of hepatitis B virus infection in the United States, 1976-1994: estimates from the National Health and Nutrition Examination Surveys. J Infect Dis. 1998; 178 954-959
13 Dimitrakopoulos A, Takou A, Haida A, Molangeli S, Gialeraki A, Kordossis T. The prevalence of hepatitis B and C in HIV-positive Greek patients: relationship to survival of deceased AIDS patients. J Infect. 2000; 40 127-131
14 Shire N J, Rouster S D, Rajicic N, Sherman K E. Occult hepatitis B in HIV-infected patients. J Acquir Immune Defic Syndr. 2004; 36 869-875
15 Rodriguez-Mendez M L, Gonzalez-Quintela A, Aguilera A, Carballo E, Barrio E. Association of HCV and HBV markers in Spanish HIV-seropositive patients in relation to risk practices. Hepatogastroenterology. 2003; 50 2093-2097
16 Centers for Disease Control and Prevention. Diagnoses of HIV/AIDS-32 States, 2000-2003. Morbid Mortal Wkly Rep MMWR. 2004; 53 1106-1110
17 Kingsley L A, Rinaldo Jr C R, Lyter D W, Valdiserri R O, Belle S H, Ho M. Sexual transmission efficiency of hepatitis B virus and human immunodeficiency virus among homosexual men. JAMA. 1990; 264 230-234
18 Scharschmidt B F, Held M J, Hollander H H et al.. Hepatitis B in patients with HIV infection: relationship to AIDS and patient survival. Ann Intern Med. 1992; 117 837-838
19 Rodriguez-Mendez M L, Gonzalez-Quintela A, Aguilera A, Barrio E. Prevalence, patterns, and course of past hepatitis B virus infection in intravenous drug users with HIV-1 infection. Am J Gastroenterol. 2000; 95 1316-1322
20 Benson C A, Kaplan J E, Masur H, Pau A, Holmes K K. Treating opportunistic infections among HIV-infected adults and adolescents. Morbid Mortal Wkly Rep MMWR. 2004; 53 54-58
21 Fattovich G, Brollo L, Giustina G et al.. Natural history and prognostic factors for chronic hepatitis type B. Gut. 1991; 32 294-298
22 Fattovich G, Giustina G, Schalm S W et al,. for the EUROHEP Study Group on Hepatitis B Virus and Cirrhosis. Occurrence of hepatocellular carcinoma and decompensation in western European patients with cirrhosis type B. Hepatology. 1995; 21 77-82
23 McMahon B J, Holck P, Bulkow L, Snowball M. Serologic and clinical outcomes of 1536 Alaska Natives chronically infected with hepatitis B virus. Ann Intern Med. 2001; 135 759-768
24 Fong T L, Di Bisceglie A M, Biswas R et al.. High levels of viral replication during acute hepatitis B infection predict progression to chronicity. J Med Virol. 1994; 43 155-158
25 Williams A L, Hoofnagle J H. Ratio of serum aspartate to alanine aminotransferase in chronic hepatitis. Relationship to cirrhosis. Gastroenterology. 1988; 95 734-739
26 Realdi G, Fattovich G, Hadziyannis S et al.. for The Investigators of the European Concerted Action on Viral Hepatitis (EUROHEP). Survival and prognostic factors in 366 patients with compensated cirrhosis type B: a multicenter study. J Hepatol. 1994; 21 656-666
27 Bodsworth N J, Cooper D A, 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
28 Hadler S C, Judson F N, O'Malley P M et al.. Outcome of hepatitis B virus infection in homosexual men and its relation to prior human immunodeficiency virus infection. J Infect Dis. 1991; 163 454-459
29 Bodsworth N, Donovan B, Nightingale B N. The effect of concurrent human immunodeficiency virus infection on chronic hepatitis B: a study of 150 homosexual men. J Infect Dis. 1989; 160 577-582
30 Koziel M. The immunopathogenesis of hepatitis B virus infection. In: Schinazi RF, Sommadossi JP, Thomas HC Therapies for Viral Hepatitis Atlanta, GA; International Medical Press 1998: 53-64
31 Perrillo R P, Regenstein F G, Roodman S T. Chronic hepatitis B in asymptomatic homosexual men with antibody to the human immunodeficiency virus. Ann Intern Med. 1986; 105 382-383
32 Bodsworth N, Donovan B, Nightingale B N. The effect of concurrent human immunodeficiency virus infection on chronic hepatitis B: a study of 150 homosexual men. J Infect Dis. 1989; 160 577-582
33 Gilson R J, Hawkins A E, Beecham M R et al.. Interactions between HIV and hepatitis B virus in homosexual men: effects on the natural history of infection. AIDS. 1997; 11 597-606
34 Colin J F, Cazals-Hatem D, Loriot M A et al.. Influence of human immunodeficiency virus infection on chronic hepatitis B in homosexual men. Hepatology. 1999; 29 1306-1310
35 Bessesen M, Ives D, Condreay L, Lawrence S, Sherman K E. Chronic active hepatitis B exacerbations in human immunodeficiency virus-infected patients following development of resistance to or withdrawal of lamivudine. Clin Infect Dis. 1999; 28 1032-1035
36 Carton J A, Maradona J A, Asensi V, Rodriguez M, Martinez A. Lamivudine for chronic hepatitis B and HIV co-infection. AIDS. 1999; 13 1002-1003
37 Dore G J, Cooper D A, Barrett C, Goh L E, Thakrar B, Atkins M. for the CAESAR Coordinating Committee . Dual efficacy of lamivudine treatment in human immunodeficiency virus/hepatitis B virus-coinfected persons in a randomized, controlled study (CAESAR). J Infect Dis. 1999; 180 607-613
38 Nagai K, Hosaka H, Kubo S, Nakamura N, Shinohara M, Nonaka H. Highly active antiretroviral therapy used to treat concurrent hepatitis B and human immunodeficiency virus infections. J Gastroenterol. 1999; 34 275-281
39 Hoff J, Bani-Sadr F, Gassin M, Raffi F. Evaluation of chronic hepatitis B virus (HBV) infection in coinfected patients receiving lamivudine as a component of anti-human immunodeficiency virus regimens. Clin Infect Dis. 2001; 32 963-969
40 Benhamou Y, Bochet M, Thibault V et al.. Long-term incidence of hepatitis B virus resistance to lamivudine in human immunodeficiency virus-infected patients. Hepatology. 1999; 30 1302-1306
41 Neau D, Schvoerer E, Robert D et al.. 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
42 Piroth L, Grappin M, Buisson M, Duong M, Portier H, Chavanet P. Hepatitis B virus seroconversion in HIV-HBV coinfected patients treated with highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2000; 23 356-357
43 Saves M, Raffi F, Clevenbergh P for the APROCO Study Group et al,. Hepatitis B or hepatitis C virus infection is a risk factor for severe hepatic cytolysis after initiation of a protease inhibitor-containing antiretroviral regimen in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother. 2000; 44 3451-3455
44 Santantonio T, Jung M C, Miska S, Pastore G, Pape G R, Will H. High prevalence and heterogeneity of HBV preC mutants in anti-HBe-positive carriers with chronic liver disease in southern Italy. J Hepatol. 1991; 13(suppl 4) S78-S81
45 Santantonio T, Jung M C, Miska S, Pastore G, Pape G R, Will H. Prevalence and type of pre-C HBV mutants in anti-HBe positive carriers with chronic liver disease in a highly endemic area. Virology. 1991; 183 840-844
46 Brunetto M R, Giarin M, Saracco G et al.. Hepatitis B virus unable to secrete e antigen and response to interferon in chronic hepatitis B. Gastroenterology. 1993; 105 845-850
47 Liang T J, Hasegawa K, Rimon N, Wands J R, Ben-Porath E. A hepatitis B virus mutant associated with an epidemic of fulminant hepatitis. N Engl J Med. 1991; 324 1705-1709
48 Liang T J, Hasegawa K, Munoz S J et al.. Hepatitis B virus precore mutation and fulminant hepatitis in the United States. A polymerase chain reaction-based assay for the detection of specific mutation. J Clin Invest. 1994; 93 550-555
49 Hofer M, Joller-Jemelka H I, Grob P J, Luthy R, Opravil M. for the Swiss HIV Cohort Study . Frequent chronic hepatitis B virus infection in HIV-infected patients positive for antibody to hepatitis B core antigen only. Eur J Clin Microbiol Infect Dis. 1998; 17 6-13
50 Vazquez-Vizoso F, Eiroa P, Ledo L, Anibarro L, Hernandez M, Ojea R. HIV infection and isolated detection of anti-HBc. Gastroenterology. 1994; 106 823-824
51 Sanchez-Quijano A, Jauregui J I, Leal M et al.. Hepatitis B virus occult infection in subjects with persistent isolated anti-HBc reactivity. J Hepatol. 1993; 17 288-293
52 Jilg W, Sieger E, Zachoval R, Schatzl H. Individuals with antibodies against hepatitis B core antigen as the only serological marker for hepatitis B infection: high percentage of carriers of hepatitis B and C virus. J Hepatol. 1995; 23 14-20
53 Nunez M, Rios P, Perez-Olmeda M, Soriano V. Lack of ‘occult’ hepatitis B virus infection in HIV-infected patients. AIDS. 2002; 16 2099-2101
54 Neau D, Winnock M, Jouvencel A C et al.. ‘Occult’ hepatitis B virus infection in HIV-infected patients with isolated antibodies to hepatitis B core antigen: Aquitaine cohort, 2002-2003. Clin Infect Dis. 2005; 40 750-753
55 Brechot C, Thiers V, Kremsdorf D, Nalpas B, Pol S, Paterlini-Brechot P. Persistent hepatitis B virus infection in subjects without hepatitis B surface antigen: clinically significant or purely “occult”?. Hepatology. 2001; 34 194-203
56 Chemin I, Zoulim F, Merle P et al.. High incidence of hepatitis B infections among chronic hepatitis cases of unknown aetiology. J Hepatol. 2001; 34 447-454
57 Mezzelani P, Quaglio G, Venturini L, Lugoboni F. for the Intersert Group of Scientific Collaboration. The significance of the isolated anti-HBc carrier. A study of 1797 drug addicts. Recenti Prog Med. 1994; 85 419-424
58 Shiota G, Oyama K, Udagawa A et al.. Occult hepatitis B virus infection in HBs antigen-negative hepatocellular carcinoma in a Japanese population: involvement of HBx and p53. J Med Virol. 2000; 62 151-158
59 Koyama H, Nishizawa Y, Kinoshita H, Fujimoto T, Morii H. Hepatocellular carcinoma with occult chronic hepatitis-hepatitis B virus as a pathogenetic factor of hepatocellular carcinoma. Osaka City Med J. 1988; 34 51-66
60 Uchida T, Shimojima S, Gotoh K, Shikata T, Mima S. Pathology of livers infected with “silent” hepatitis B virus mutant. Liver. 1994; 14 251-256
61 Takeuchi M, Fujimoto J, Niwamoto H, Yamamoto Y, Okamoto E. Frequent detection of hepatitis B virus X-gene DNA in hepatocellular carcinoma and adjacent liver tissue in hepatitis B surface antigen-negative patients. Dig Dis Sci. 1997; 42 2264-2269
62 Paterlini P, Poussin K, Kew M, Franco D, Brechot C. Selective accumulation of the X transcript of hepatitis B virus in patients negative for hepatitis B surface antigen with hepatocellular carcinoma. Hepatology. 1995; 21 313-321
63 Thiers V, Nakajima E, Kremsdorf D et al.. Transmission of hepatitis B from hepatitis-B-seronegative subjects. Lancet. 1988; 2 1273-1276
64 Hoofnagle J H, Seefe L B, Bales Z B, Zimmerman H J. Type B hepatitis after transfusion with blood containing antibody to hepatitis B core antigen. N Engl J Med. 1978; 298 1379-1383
65 Scully L J, Sung H, Pennie R, Gill P. Detection of hepatitis B virus DNA in the serum of Canadian hepatitis B surface antigen negative, anti-HBc positive individuals, using the polymerase chain reaction. J Med Virol. 1994; 44 293-297
66 Luo K X, Zhou R, He C, Liang Z S, Jiang S B. Hepatitis B virus DNA in sera of virus carriers positive exclusively for antibodies to the hepatitis B core antigen. J Med Virol. 1991; 35 55-59
67 Kao J H, Chen P J, Lai M Y, Chen D S. Occult hepatitis B virus infection and clinical outcomes of patients with chronic hepatitis C. J Clin Microbiol. 2002; 40 4068-4071
68 Soriano V, Puoti M, Bonacini M et al.. Care of patients with chronic hepatitis B and HIV co-infection: recommendations from an HIV-HBV International Panel. AIDS. 2005; 19 221-240
69 Soriano V, Miro J M, Garcia-Samaniego J et al.. Consensus conference on chronic viral hepatitis and HIV infection: updated Spanish recommendations. J Viral Hepat. 2004; 11 2-17
70 McDonald J A, Caruso L, Karayiannis P et al.. Diminished responsiveness of male homosexual chronic hepatitis B virus carriers with HTLV-III antibodies to recombinant alpha-interferon. Hepatology. 1987; 7 719-723
71 Brook M G, Karayiannis P, Thomas H C. Which patients with chronic hepatitis B virus infection will respond to alpha-interferon therapy? A statistical analysis of predictive factors. Hepatology. 1989; 10 761-763
72 Zinkernagel R M. Immunity, immunopathology and vaccines against HIV?. Vaccine. 2002; 20 1913-1917
73 Di Martino V, Thevenot T, Colin J F et al.. Influence of HIV infection on the response to interferon therapy and the long-term outcome of chronic hepatitis B. Gastroenterology. 2002; 123 1812-1822
74 Katlama C, Ingrand D, Loveday C for the Lamivudine European HIV Working Group et al,. Safety and efficacy of lamivudine-zidovudine combination therapy in antiretroviral-naive patients. A randomized controlled comparison with zidovudine monotherapy. JAMA. 1996; 276 118-125
75 Benhamou Y, Katlama C, Lunel F et al.. Effects of lamivudine on replication of hepatitis B virus in HIV-infected men. Ann Intern Med. 1996; 125 705-712
76 Benhamou Y, Bochet M, Thibault V et al.. Long-term incidence of hepatitis B virus resistance to lamivudine in human immunodeficiency virus-infected patients. Hepatology. 1999; 30 1302-1306
77 Wolters L M, Niesters H G, Hansen B E et al.. Development of hepatitis B virus resistance for lamivudine in chronic hepatitis B patients co-infected with the human immunodeficiency virus in a Dutch cohort. J Clin Virol. 2002; 24 173-181
78 Bonacini M, Kurz A, Locarnini S, Ayres A, Gibbs C. Fulminant hepatitis B due to a lamivudine-resistant mutant of HBV in a patient coinfected with HIV. Gastroenterology. 2002; 122 244-245
79 Benhamou Y, Bochet M, Thibault V et al.. Safety and efficacy of adefovir dipivoxil in patients co-infected with HIV-1 and lamivudine-resistant hepatitis B virus: an open-label pilot study. Lancet. 2001; 358 718-723
80 Delaugerre C, Marcelin A G, Thibault V et al.. Human immunodeficiency virus (HIV) Type 1 reverse transcriptase resistance mutations in hepatitis B virus (HBV)-HIV-coinfected patients treated for HBV chronic infection once daily with 10 milligrams of adefovir dipivoxil combined with lamivudine. Antimicrob Agents Chemother. 2002; 46 1586-1588
81 Nelson M, Portsmouth S, Stebbing J et al.. An open-label study of tenofovir in HIV-1 and hepatitis B virus co-infected individuals. AIDS. 2003; 17 F7-F10
82 Dore G J, Cooper D A, Pozniak A L et al.. Efficacy of tenofovir disoproxil fumarate in antiretroviral therapy-naive and -experienced patients coinfected with HIV-1 and hepatitis B virus. J Infect Dis. 2004; 189 1185-1192
83 Bani-Sadr F, Palmer P, Scieux C, Molina J M. Ninety-six-week efficacy of combination therapy with lamivudine and tenofovir in patients coinfected with HIV-1 and wild-type hepatitis B virus. Clin Infect Dis. 2004; 39 1062-1064
84 Peters M G, Anderson J, Lynch P et al.. Tenofovir disoproxil fumarate is not inferior to adefovir dipivoxil for the treatment of hepatitis B virus in subjects who are coinfected with HIV: results of ACTG A5127. Paper presented at: 12th Conference on Retroviruses and Opportunistic Infections: Foundation for Retrovirology and Human Health. February 22-25, 2005 Boston, MA; http://Available at: www.retroconference.org/Search_Abstract_2005/AbstractSearch.aspx
85 de Man R A, Wolters L M, Nevens F et al.. Safety and efficacy of oral entecavir given for 28 days in patients with chronic hepatitis B virus infection. Hepatology. 2001; 34 578-582
86 Lai C L, Rosmawati M, Lao J et al.. Entecavir is superior to lamivudine in reducing hepatitis B virus DNA in patients with chronic hepatitis B infection. Gastroenterology. 2002; 123 1831-1838
87 Tenney D J, Levine S M, Rose R E et al.. Clinical emergence of entecavir-resistant hepatitis B virus requires additional substitutions in virus already resistant to lamivudine. Antimicrob Agents Chemother. 2004; 48 3498-3507
88 Pessoa W, Gazzard B, Huang A et al.. Entecavir in HIV/HBV-co-infected patients: safety and efficacy in a phase II study (ETV-038) (abst 123). Presented at: 12th Conference on Retroviruses and Opportunistic Infections February 22-25, 2005 Boston, MA; http://Available at: www.retroconference.org/2005/CD/Abstracts/25104.htm
89 Marcellin P, Bernuau J, Martinot-Peignoux M et al.. Prevalence of hepatitis C virus infection in asymptomatic anti-HIV1 negative pregnant women and their children. Dig Dis Sci. 1993; 38 2151-2155

Norah J Shire

The University of Cincinnati, Division of Digestive Diseases

231 Albert Sabin Way, ML 0595

Cincinnati, OH 45267-0595

Email: norah.shire@uc.edu