Epidemiology, clinical manifestations, and diagnosis of hepatitis B in the HIV-infected patient
- Kenneth E Sherman, MD, PhD
Kenneth E Sherman, MD, PhD
- Professor of Medicine
- University of Cincinnati College of Medicine
- Chloe L Thio, MD
Chloe L Thio, MD
- Professor of Medicine
- Johns Hopkins University
The worldwide epidemics of hepatitis B and HIV have led to new understanding of the complicated interactions between these two viruses. Coinfection with HIV has a major impact on the natural history, diagnosis, progression, and morbidity and mortality related to hepatitis B virus (HBV) infection. The presence of chronic hepatitis B can also lead to an increased risk of hepatotoxicity related to the administration of potent antiretroviral therapy (ART).
The epidemiology, clinical manifestations, and diagnosis of hepatitis B in the HIV-infected patient will be reviewed here. Treatment and prevention as well as issues related to hepatitis C and HIV coinfection are discussed separately. (See "Treatment of chronic hepatitis B in the HIV-infected patient" and "Prevention of hepatitis B virus infection in the HIV-infected adult" and "Epidemiology, natural history, and diagnosis of hepatitis C in the HIV-infected patient" and "Evaluation of the HIV-infected patient with chronic hepatitis C virus infection".)
Hepatitis B virus (HBV) and HIV are often diagnosed in the same patient because they share similar routes of transmission. Chronic HBV affects approximately 10 percent of HIV-infected patients worldwide  and a study of 16,248 HIV-infected patients in the United States found the prevalence of chronic HBV was 8 percent among unvaccinated participants .
However, the rates of HIV/HBV coinfection vary according to geographic region and are highest in sub-Saharan Africa and Asia, where most transmission occurs perinatally. In developed countries, laboratory markers of prior HBV infection are more common in men who have sex with men (MSM) and injection drug users [2-4].
DIAGNOSIS OF CHRONIC HBV INFECTION
HIV-infected patients should have routine testing for Hepatitis B virus (HBV) infection [5,6]. The diagnosis of chronic hepatitis B is made the same way in HIV-infected patients as in HIV-seronegative patients . A detailed discussion on the diagnosis of HBV infection is found elsewhere and is summarized below. (See "Diagnosis of hepatitis B virus infection".)
- Puoti M, Airoldi M, Bruno R, et al. Hepatitis B virus co-infection in human immunodeficiency virus-infected subjects. AIDS Rev 2002; 4:27.
- Kellerman SE, Hanson DL, McNaghten AD, Fleming PL. Prevalence of chronic hepatitis B and incidence of acute hepatitis B infection in human immunodeficiency virus-infected subjects. J Infect Dis 2003; 188:571.
- Rodríguez-Méndez ML, González-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.
- McGovern BH. The epidemiology, natural history and prevention of hepatitis B: implications of HIV coinfection. Antivir Ther 2007; 12 Suppl 3:H3.
- Thio CL. Diagnosis, diagnostic tests and monitoring of hepatitis B virus in monoinfected and HIV-coinfected patients. Antivir Ther 2007; 12 Suppl 3:H25.
- Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf (Accessed on September 21, 2016).
- Koziel MJ, Peters MG. Viral hepatitis in HIV infection. N Engl J Med 2007; 356:1445.
- http://www.aasld.org/practiceguidelines/Documents/Bookmarked%20Practice%20Guidelines/Chronic_Hep_B_Update_2009%208_24_2009.pdf (Accessed on February 18, 2011).
- Iloeje UH, Yang HI, Su J, et al. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology 2006; 130:678.
- Chen CF, Lee WC, Yang HI, et al. Changes in serum levels of HBV DNA and alanine aminotransferase determine risk for hepatocellular carcinoma. Gastroenterology 2011; 141:1240.
- Kucirka LM, Farzadegan H, Feld JJ, et al. Prevalence, correlates, and viral dynamics of hepatitis delta among injection drug users. J Infect Dis 2010; 202:845.
- Jain MK, Opio CK, Osuagwu CC, et al. Do HIV care providers appropriately manage hepatitis B in coinfected patients treated with antiretroviral therapy? Clin Infect Dis 2007; 44:996.
- Henke-Gendo C, Amini-Bavil-Olyaee S, Challapalli D, et al. 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.
- Neau D, Winnock M, Jouvencel AC, 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.
- Gandhi RT, Wurcel A, Lee H, et al. Isolated antibody to hepatitis B core antigen in human immunodeficiency virus type-1-infected individuals. Clin Infect Dis 2003; 36:1602.
- Witt MD, Lewis RJ, Rieg G, et al. Predictors of the isolated hepatitis B core antibody pattern in HIV-infected and -uninfected men in the multicenter AIDS cohort study. Clin Infect Dis 2013; 56:606.
- French AL, Operskalski E, Peters M, et al. Isolated hepatitis B core antibody is associated with HIV and ongoing but not resolved hepatitis C virus infection in a cohort of US women. J Infect Dis 2007; 195:1437.
- Gandhi RT, Wurcel A, McGovern B, et al. Low prevalence of ongoing hepatitis B viremia in HIV-positive individuals with isolated antibody to hepatitis B core antigen. J Acquir Immune Defic Syndr 2003; 34:439.
- Sheng WH, Kao JH, Chen PJ, et al. Evolution of hepatitis B serological markers in HIV-infected patients receiving highly active antiretroviral therapy. Clin Infect Dis 2007; 45:1221.
- French AL, Lin MY, Evans CT, et al. Long-term serologic follow-up of isolated hepatitis B core antibody in HIV-infected and HIV-uninfected women. Clin Infect Dis 2009; 49:148.
- Vivekanandan P, Kannangai R, Ray SC, et al. Comprehensive genetic and epigenetic analysis of occult hepatitis B from liver tissue samples. Clin Infect Dis 2008; 46:1227.
- Schmeltzer P, Sherman KE. Occult hepatitis B: clinical implications and treatment decisions. Dig Dis Sci 2010; 55:3328.
- Hofer M, Joller-Jemelka HI, Grob PJ, et al. Frequent chronic hepatitis B virus infection in HIV-infected patients positive for antibody to hepatitis B core antigen only. Swiss HIV Cohort Study. Eur J Clin Microbiol Infect Dis 1998; 17:6.
- Shire NJ, Rouster SD, Stanford SD, et al. The prevalence and significance of occult hepatitis B virus in a prospective cohort of HIV-infected patients. J Acquir Immune Defic Syndr 2007; 44:309.
- Rehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol 2005; 5:215.
- Thimme R, Wieland S, Steiger C, et al. CD8(+) T cells mediate viral clearance and disease pathogenesis during acute hepatitis B virus infection. J Virol 2003; 77:68.
- Kawatani T, Suou T, Tajima F, et al. Incidence of hepatitis virus infection and severe liver dysfunction in patients receiving chemotherapy for hematologic malignancies. Eur J Haematol 2001; 67:45.
- Martel N, Cotte L, Trabaud MA, et al. Probable corticosteroid-induced reactivation of latent hepatitis B virus infection in an HIV-positive patient involving immune escape. J Infect Dis 2012; 205:1757.
- Tsai SL, Chen PJ, Lai MY, et al. Acute exacerbations of chronic type B hepatitis are accompanied by increased T cell responses to hepatitis B core and e antigens. Implications for hepatitis B e antigen seroconversion. J Clin Invest 1992; 89:87.
- Boni C, Bertoletti A, Penna A, et al. Lamivudine treatment can restore T cell responsiveness in chronic hepatitis B. J Clin Invest 1998; 102:968.
- Revill PA, Littlejohn M, Ayres A, et al. Identification of a novel hepatitis B virus precore/core deletion mutant in HIV/hepatitis B virus co-infected individuals. AIDS 2007; 21:1701.
- Ferrari C, Bertoletti A, Penna A, et al. Identification of immunodominant T cell epitopes of the hepatitis B virus nucleocapsid antigen. J Clin Invest 1991; 88:214.
- Colin JF, Cazals-Hatem D, Loriot MA, et al. Influence of human immunodeficiency virus infection on chronic hepatitis B in homosexual men. Hepatology 1999; 29:1306.
- Gilson RJ, Hawkins AE, Beecham MR, et al. Interactions between HIV and hepatitis B virus in homosexual men: effects on the natural history of infection. AIDS 1997; 11:597.
- Manegold C, Hannoun C, Wywiol A, et al. Reactivation of hepatitis B virus replication accompanied by acute hepatitis in patients receiving highly active antiretroviral therapy. Clin Infect Dis 2001; 32:144.
- Mills CT, Lee E, Perrillo R. Relationship between histology, aminotransferase levels, and viral replication in chronic hepatitis B. Gastroenterology 1990; 99:519.
- Di Martino V, Thevenot T, Colin JF, 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.
- Bodsworth N, Donovan B, Nightingale BN. The effect of concurrent human immunodeficiency virus infection on chronic hepatitis B: a study of 150 homosexual men. J Infect Dis 1989; 160:577.
- Vento S, Di Perri G, Garofano T, et al. Reactivation of hepatitis B in AIDS. Lancet 1989; 2:108.
- Piroth L, Sène D, Pol S, et al. Epidemiology, diagnosis and treatment of chronic hepatitis B in HIV-infected patients (EPIB 2005 STUDY). AIDS 2007; 21:1323.
- Hadler SC, Judson FN, O'Malley PM, 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.
- Thio CL, Seaberg EC, Skolasky R Jr, et al. HIV-1, hepatitis B virus, and risk of liver-related mortality in the Multicenter Cohort Study (MACS). Lancet 2002; 360:1921.
- Puoti M, Spinetti A, Ghezzi A, et al. Mortality for liver disease in patients with HIV infection: a cohort study. J Acquir Immune Defic Syndr 2000; 24:211.
- 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.
- Bräu N, Fox RK, Xiao P, et al. Presentation and outcome of hepatocellular carcinoma in HIV-infected patients: a U.S.-Canadian multicenter study. J Hepatol 2007; 47:527.
- Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 2006; 295:65.
- Yu MW, Yeh SH, Chen PJ, et al. Hepatitis B virus genotype and DNA level and hepatocellular carcinoma: a prospective study in men. J Natl Cancer Inst 2005; 97:265.
- Thio CL. Hepatitis B and human immunodeficiency virus coinfection. Hepatology 2009; 49:S138.
- Puoti M, Torti C, Bruno R, et al. Natural history of chronic hepatitis B in co-infected patients. J Hepatol 2006; 44:S65.
- Housset C, Pol S, Carnot F, et al. Interactions between human immunodeficiency virus-1, hepatitis delta virus and hepatitis B virus infections in 260 chronic carriers of hepatitis B virus. Hepatology 1992; 15:578.
- McDonald JA, Harris S, Waters JA, Thomas HC. Effect of human immunodeficiency virus (HIV) infection on chronic hepatitis B hepatic viral antigen display. J Hepatol 1987; 4:337.
- Sheng WH, Hung CC, Kao JH, et al. Impact of hepatitis D virus infection on the long-term outcomes of patients with hepatitis B virus and HIV coinfection in the era of highly active antiretroviral therapy: a matched cohort study. Clin Infect Dis 2007; 44:988.
- Eskild A, Magnus P, Petersen G, et al. Hepatitis B antibodies in HIV-infected homosexual men are associated with more rapid progression to AIDS. AIDS 1992; 6:571.
- Twu SJ, Detels R, Nelson K, et al. Relationship of hepatitis B virus infection to human immunodeficiency virus type 1 infection. J Infect Dis 1993; 167:299.
- Thio CL, Smeaton L, Saulynas M, et al. Characterization of HIV-HBV coinfection in a multinational HIV-infected cohort. AIDS 2013; 27:191.
- Idoko J, Meloni S, Muazu M, et al. Impact of hepatitis B virus infection on human immunodeficiency virus response to antiretroviral therapy in Nigeria. Clin Infect Dis 2009; 49:1268.
- Chun HM, Roediger MP, Hullsiek KH, et al. Hepatitis B virus coinfection negatively impacts HIV outcomes in HIV seroconverters. J Infect Dis 2012; 205:185.
- Scharschmidt BF, Held MJ, Hollander HH, et al. Hepatitis B in patients with HIV infection: relationship to AIDS and patient survival. Ann Intern Med 1992; 117:837.
- Sinicco A, Raiteri R, Sciandra M, et al. The influence of cytomegalovirus on the natural history of HIV infection: evidence of rapid course of HIV infection in HIV-positive patients infected with cytomegalovirus. Scand J Infect Dis 1997; 29:543.
- Nikolopoulos GK, Paraskevis D, Hatzitheodorou E, et al. Impact of hepatitis B virus infection on the progression of AIDS and mortality in HIV-infected individuals: a cohort study and meta-analysis. Clin Infect Dis 2009; 48:1763.
- Hoffmann CJ, Seaberg EC, Young S, et al. Hepatitis B and long-term HIV outcomes in coinfected HAART recipients. AIDS 2009; 23:1881.
- Chun HM, Mesner O, Thio CL, et al. HIV outcomes in Hepatitis B virus coinfected individuals on HAART. J Acquir Immune Defic Syndr 2014; 66:197.
- Crane M, Oliver B, Matthews G, et al. Immunopathogenesis of hepatic flare in HIV/hepatitis B virus (HBV)-coinfected individuals after the initiation of HBV-active antiretroviral therapy. J Infect Dis 2009; 199:974.
- den Brinker M, Wit FW, Wertheim-van Dillen PM, et al. Hepatitis B and C virus co-infection and the risk for hepatotoxicity of highly active antiretroviral therapy in HIV-1 infection. AIDS 2000; 14:2895.
- Lascar RM, Lopes AR, Gilson RJ, et al. Effect of HIV infection and antiretroviral therapy on hepatitis B virus (HBV)-specific T cell responses in patients who have resolved HBV infection. J Infect Dis 2005; 191:1169.
- Lascar RM, Gilson RJ, Lopes AR, et al. Reconstitution of hepatitis B virus (HBV)-specific T cell responses with treatment of human immunodeficiency virus/HBV coinfection. J Infect Dis 2003; 188:1815.
- Carr A, Cooper DA. Restoration of immunity to chronic hepatitis B infection in HIV-infected patient on protease inhibitor. Lancet 1997; 349:995.
- Drake A, Mijch A, Sasadeusz J. Immune reconstitution hepatitis in HIV and hepatitis B coinfection, despite lamivudine therapy as part of HAART. Clin Infect Dis 2004; 39:129.
- Sulkowski MS, Mehta SH, Chaisson RE, et al. Hepatotoxicity associated with protease inhibitor-based antiretroviral regimens with or without concurrent ritonavir. AIDS 2004; 18:2277.
- Sulkowski MS, Thomas DL, Mehta SH, et al. Hepatotoxicity associated with nevirapine or efavirenz-containing antiretroviral therapy: role of hepatitis C and B infections. Hepatology 2002; 35:182.
- Sulkowski MS. Drug-induced liver injury associated with antiretroviral therapy that includes HIV-1 protease inhibitors. Clin Infect Dis 2004; 38 Suppl 2:S90.
- Wit FW, Weverling GJ, Weel J, et al. Incidence of and risk factors for severe hepatotoxicity associated with antiretroviral combination therapy. J Infect Dis 2002; 186:23.
- DIAGNOSIS OF CHRONIC HBV INFECTION
- Isolated anti-HB core antibody
- Occult HBV
- Immunologic factors
- Virologic factors
- HIV AND NATURAL HISTORY OF HBV INFECTION
- HIV AND LIVER DISEASE PROGRESSION
- EFFECT OF HIV ON LIVER-RELATED MORTALITY
- EFFECT OF HBV ON HIV PROGRESSION
- EFFECT OF HBV ON ALL CAUSE MORTALITY
- HBV AND IMMUNE RECONSTITUTION
- HBV AND RISK OF DRUG INDUCED HEPATOTOXICITY
- SUMMARY AND RECOMMENDATIONS