HIV coinfection with hepatitis b

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Ujjwal Rastogi, MBBS [2]

Overview

Coinfection with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) is common due to shared routes of transmission. The impact of coinfection is especially important in regions with widespread use of ART.[1] As the use of ART becomes more prevalent in parts of the world with high HBV endemicity and long term survival increases, it is likely that liver disease from chronic hepatitis B in HIV-infected population may emerge as a greater public health problem than before.[1]

Epidemiology

In areas of low endemicity, such as North America, Australia and Europe, HBV and HIV infection are usually acquired in adulthood through sexual or percutaneous transmission. In areas of low endemicity, the prevalence of chronic coinfection is around 5-7% among HIV-infected individuals.[2] In countries with intermediate and high HBV endemicity, the main routes of transmission of HBV are perinatal or in early childhood; in these countries HBV coinfection rates are 10-20%.[3][4][5]

Natural History

The rate of progression and complications from viral hepatitis are accelerated in patients with HIV coinfection.[6][7] After acquiring HBV infection, HIV infected individuals are 6 times more likely to develop chronic hepatitis B than HIV negative individuals.[8][9][10] This was more likely to occur in HIV infected men with lower CD4 cells. Decreased rates of clearance of HBeAg and increased HBV replication are also seen, with higher HBV DNA viral load.[11][12][13] In addition, HIV infected individuals are more likely to lose previously developed protective anti-HBs antibody and develop acute hepatitis B infection; This risk is also associated with lower CD4 counts.[14][15]

HIV also hastens the progression of HBV related liver disease. Cirrhosis is more common despite lower ALT levels than in HBV mono-infection and is also more common with lower CD4 counts.[11][16]

Complications

Following initiation of antiretroviral therapy (ART), immune reconstitution inflammatory syndrome (IRIS) may occur which can lead to worsening liver disease including hepatic decompensation. In addition, after discontinuation of an ART regimen containing anti-HBV agents, reactivation of hepatitis B can occur. ALT elevations occurred in 29% of 147 patients within 6 months of withdrawal.[17] If reactivation occurs, resuming an agent that is active against HBV is required.

HIV-HBV coinfected men are greater than 17 times more likely to die of liver related causes compared to those mono-infected with HBV.[18] For individuals on ART, coinfection with chronic hepatitis B increases the risk of hepatotoxicity from ART three-fold to five-fold.[19][20][21]

It is unclear at present if the risk of hepatocellular carcinoma (HCC) is increased, but there is some evidence that HIV infected individuals with lower CD4 counts are at greater risk of developing HCC.[22]

Diagnosis

Accurate assessment of HBV infection in HIV co-infected individuals is necessary in order to base therapeutic decisions. [7]

WHO advocates HBsAg testing especially in areas of high HBV prevalence; but additional testing for HBV markers such as HBeAg and HBV DNA and to assess stage of liver disease (e.g. liver enzymes, liver biopsy) may not be widely available in many resource limited countries.

Liver biopsy remains the gold standard for assessing disease severity in HIV-HBV coinfection. Non-invasive markers are also available but none have been widely studied in co-infected patients.

Hoffman and Thio provided management recommendations for use in areas with limited resources. They recommend that HBsAg and liver enzymes be tested before ART, with liver enzymes being repeated once or twice during the first 3 months after commencing ART. Detection of HBV DNA is helpful but may not be available. Chronic HBV carriers with HBeAg positivity may benefit from starting anti-HBV therapy early. [1]

Screening

For HIV infected individuals with chronic HBV, additional screening for coinfection with HCV is recommended; hepatocellular carcinoma screening with alpha fetoprotein and imaging of liver every 6 months is being suggested by some but the cost benefit of one or both tests as well as the frequency of monitoring in various health economies remain to be assessed. [7]

Treatment

Treatment is most beneficial for those in the immunoactive phase of chronic hepatitis B (characterized by liver enzyme elevations, fluctuating HBV DNA levels and pronounced hepatic necro-inflammation) [1]

Patient characteristics that favour treatment success are [23]

  • Low HBV DNA levels.
  • HBeAg positivity.
  • Evidence of liver inflammation based on liver biopsy findings.
  • Liver enzyme elevations.

It is unknown if this applies to HIV co-infected individuals who have higher HBV DNA and lower liver enzyme elevations but more cirrhosis and therefore the optimum time to commence treatment in HIV-HBV co-infected individuals is unclear at present.

The treatment and management of co-infected individuals requires modification in resource poor countries due to limited availability of some HBV tests as well as therapeutic agents for treatment of HIV and HBV. 3TC is widely available and tenofovir and adefovir have limited availability.

Current Regimen

Goals of treatment

HIV:Treatment for HIV has resulted in a marked reduction in AIDS-related mortality. As a result, liver disease from HBV and HCV is now becoming a major cause of morbidity and mortality in HIV infected patients.[24] Therefore the goal of treatment is to optimize anti-HIV therapy in HIV/HBV co-infected patients to improve and/or preserve immune function and reduce HIV associated morbidity and mortality.

HBV: In mono-infected patients, HBV therapy can reduce the risk of developing complications of liver disease.[25] [26] Natural history studies of chronically infected individuals have linked the risk of progression to cirrhosis and HCC to ongoing HBV replication.[27][28][29] In addition, treatment for HBV has been directed at reducing replicating virus. It has been demonstrated that the degree of HBV viral suppression achieved during treatment appears to be the most important determinant of treatment outcomes [30][31], but HBV DNA levels as low as 2000 IU/mL is still associated with disease progression.[32][33] Recent recommendations have advocated for undetectable HBV DNA as the therapeutic goal with the overall goal of therapy being to reduce 5 progression to cirrhosis, liver failure, HCC and need for liver transplantation.[34][35]

Reference

  1. ↑ 1.0 1.1 1.2 1.3 Hoffmann CJ, Thio CL (2007). "Clinical implications of HIV and hepatitis B co-infection in Asia and Africa". Lancet Infect Dis. 7 (6): 402–9. doi:10.1016/S1473-3099(07)70135-4. PMID 17521593. Retrieved 2012-03-29. Unknown parameter |month= ignored (help)
  2. ↑ Alter MJ (2006). "Epidemiology of viral hepatitis and HIV co-infection". J. Hepatol. 44 (1 Suppl): S6–9. doi:10.1016/j.jhep.2005.11.004. PMID 16352363. Retrieved 2012-03-29.
  3. ↑ Lee HC, Ko NY, Lee NY, Chang CM, Ko WC (2008). "Seroprevalence of viral hepatitis and sexually transmitted disease among adults with recently diagnosed HIV infection in Southern Taiwan, 2000-2005: upsurge in hepatitis C virus infections among injection drug users". J. Formos. Med. Assoc. 107 (5): 404–11. doi:10.1016/S0929-6646(08)60106-0. PMID 18492625. Retrieved 2012-03-29. Unknown parameter |month= ignored (help)
  4. ↑ Nyirenda M, Beadsworth MB, Stephany P, Hart CA, Hart IJ, Munthali C, Beeching NJ, Zijlstra EE (2008). "Prevalence of infection with hepatitis B and C virus and coinfection with HIV in medical inpatients in Malawi". J. Infect. 57 (1): 72–7. doi:10.1016/j.jinf.2008.05.004. PMID 18555534. Retrieved 2012-03-29. Unknown parameter |month= ignored (help)
  5. ↑ Diop-Ndiaye H, Touré-Kane C, Etard JF, Lô G, Diaw P, Ngom-Gueye NF, Gueye PM, Ba-Fall K, Ndiaye I, Sow PS, Delaporte E, Mboup S (2008). "Hepatitis B, C seroprevalence and delta viruses in HIV-1 Senegalese patients at HAART initiation (retrospective study)". J. Med. Virol. 80 (8): 1332–6. doi:10.1002/jmv.21236. PMID 18551596. Retrieved 2012-03-29. Unknown parameter |month= ignored (help)
  6. ↑ Puoti M, Cozzi-Lepri A, Paraninfo G, Arici C, Moller NF, Lundgren JD, Ledergerber B, Rickenbach M, Suarez-Lozano I, Garrido M, Dabis F, Winnock M, Milazzo L, Gervais A, Raffi F, Gill J, Rockstroh J, Ourishi N, Mussini C, Castagna A, De Luca A, Monforte A (2006). "Impact of lamivudine on the risk of liver-related death in 2,041 HBsAg- and HIV-positive individuals: results from an inter-cohort analysis". Antivir. Ther. (Lond.). 11 (5): 567–74. PMID 16964824. |access-date= requires |url= (help)
  7. ↑ 7.0 7.1 7.2 Thio CL (2009). "Hepatitis B and human immunodeficiency virus coinfection". Hepatology. 49 (5 Suppl): S138–45. doi:10.1002/hep.22883. PMID 19399813. Retrieved 2012-03-29. Unknown parameter |month= ignored (help)
  8. ↑ Bodsworth NJ, Cooper DA, Donovan B (1991). "The influence of human immunodeficiency virus type 1 infection on the development of the hepatitis B virus carrier state". J. Infect. Dis. 163 (5): 1138–40. PMID 2019762. Retrieved 2012-03-29. Unknown parameter |month= ignored (help)
  9. ↑ Hadler SC, Judson FN, O'Malley PM, Altman NL, Penley K, Buchbinder S, Schable CA, Coleman PJ, Ostrow DN, Francis DP (1991). "Outcome of hepatitis B virus infection in homosexual men and its relation to prior human immunodeficiency virus infection". J. Infect. Dis. 163 (3): 454–9. PMID 1825315. Retrieved 2012-03-29. Unknown parameter |month= ignored (help)
  10. ↑ Gatanaga H, Yasuoka A, Kikuchi Y, Tachikawa N, Oka S (2000). "Influence of prior HIV-1 infection on the development of chronic hepatitis B infection". Eur. J. Clin. Microbiol. Infect. Dis. 19 (3): 237–9. PMID 10795602. Retrieved 2012-03-29. Unknown parameter |month= ignored (help)
  11. ↑ 11.0 11.1 Colin JF, Cazals-Hatem D, Loriot MA, Martinot-Peignoux M, Pham BN, Auperin A, Degott C, Benhamou JP, Erlinger S, Valla D, Marcellin P (1999). "Influence of human immunodeficiency virus infection on chronic hepatitis B in homosexual men". Hepatology. 29 (4): 1306–10. doi:10.1002/hep.510290447. PMID 10094979. Retrieved 2012-03-29. Unknown parameter |month= ignored (help)
  12. ↑ Gilson RJ, Hawkins AE, Beecham MR, Ross E, Waite J, Briggs M, McNally T, Kelly GE, Tedder RS, Weller IV (1997). "Interactions between HIV and hepatitis B virus in homosexual men: effects on the natural history of infection". AIDS. 11 (5): 597–606. PMID 9108941. Retrieved 2012-03-29. Unknown parameter |month= ignored (help)
  13. ↑ Krogsgaard K, Lindhardt BO, Nielson JO, Andersson P, Kryger P, Aldershvile J, Gerstoft J, Pedersen C (1987). "The influence of HTLV-III infection on the natural history of hepatitis B virus infection in male homosexual HBsAg carriers". Hepatology. 7 (1): 37–41. PMID 3643160. |access-date= requires |url= (help)
  14. ↑ Biggar RJ, Goedert JJ, Hoofnagle J (1987). "Accelerated loss of antibody to hepatitis B surface antigen among immunodeficient homosexual men infected with HIV". N. Engl. J. Med. 316 (10): 630–1. doi:10.1056/NEJM198703053161015. PMID 3807959. Retrieved 2012-03-29. Unknown parameter |month= ignored (help)
  15. ↑ Laukamm-Josten U, Müller O, Bienzle U, Feldmeier H, Uy A, Guggenmoos-Holzmann I (1988). "Decline of naturally acquired antibodies to hepatitis B surface antigen in HIV-1 infected homosexual men". AIDS. 2 (5): 400–1. PMID 3146272. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  16. ↑ Di Martino V, Thevenot T, Colin JF, Boyer N, Martinot M, Degos F, Coulaud JP, Vilde JL, Vachon F, Degott C, Valla D, Marcellin P (2002). "Influence of HIV infection on the response to interferon therapy and the long-term outcome of chronic hepatitis B". Gastroenterology. 123 (6): 1812–22. doi:10.1053/gast.2002.37061. PMID 12454838. Retrieved 2012-03-29. Unknown parameter |month= ignored (help)
  17. ↑ Bellini C, Keiser O, Chave JP, Evison J, Fehr J, Kaiser L, Weber R, Vernazza P, Bernasconi E, Telenti A, Cavassini M (2009). "Liver enzyme elevation after lamivudine withdrawal in HIV-hepatitis B virus co-infected patients: the Swiss HIV Cohort Study". HIV Med. 10 (1): 12–8. doi:10.1111/j.1468-1293.2008.00646.x. PMID 18795964. Retrieved 2012-03-29. Unknown parameter |month= ignored (help)
  18. ↑ Thio CL, Seaberg EC, Skolasky R, Phair J, Visscher B, Muñoz A, Thomas DL (2002). "HIV-1, hepatitis B virus, and risk of liver-related mortality in the Multicenter Cohort Study (MACS)". Lancet. 360 (9349): 1921–6. PMID 12493258. Retrieved 2012-03-29. Unknown parameter |month= ignored (help)
  19. ↑ Puoti M, Torti C, Ripamonti D, Castelli F, Zaltron S, Zanini B, Spinetti A, Putzolu V, Casari S, Tomasoni L, Quiros-Roldan E, Favret M, Berchich L, Grigolato P, Callea F, Carosi G (2003). "Severe hepatotoxicity during combination antiretroviral treatment: incidence, liver histology, and outcome". J. Acquir. Immune Defic. Syndr. 32 (3): 259–67. PMID 12626885. Retrieved 2012-03-29. Unknown parameter |month= ignored (help)
  20. ↑ Sulkowski MS, Thomas DL, Chaisson RE, Moore RD (2000). "Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection". JAMA. 283 (1): 74–80. PMID 10632283. Retrieved 2012-03-29. Unknown parameter |month= ignored (help)
  21. ↑ Livry C, Binquet C, Sgro C, Froidure M, Duong M, Buisson M, Grappin M, Quantin C, Portier H, Chavanet P, Piroth L (2003). "Acute liver enzyme elevations in HIV-1-infected patients". HIV Clin Trials. 4 (6): 400–10. PMID 14628283. Retrieved 2012-03-29.
  22. ↑ Clifford GM, Rickenbach M, Polesel J, Dal Maso L, Steffen I, Ledergerber B, Rauch A, Probst-Hensch NM, Bouchardy C, Levi F, Franceschi S (2008). "Influence of HIV-related immunodeficiency on the risk of hepatocellular carcinoma". AIDS. 22 (16): 2135–41. doi:10.1097/QAD.0b013e32831103ad. PMID 18832877. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  23. ↑ Soriano V, Puoti M, Bonacini M, Brook G, Cargnel A, Rockstroh J, Thio C, Benhamou Y (2005). "Care of patients with chronic hepatitis B and HIV co-infection: recommendations from an HIV-HBV International Panel". AIDS. 19 (3): 221–40. PMID 15718833. Retrieved 2012-03-30. Unknown parameter |month= ignored (help)
  24. ↑ Puoti M, Spinetti A, Ghezzi A, Donato F, Zaltron S, Putzolu V, Quiros-Roldan E, Zanini B, Casari S, Carosi G (2000). "Mortality for liver disease in patients with HIV infection: a cohort study". J. Acquir. Immune Defic. Syndr. 24 (3): 211–7. PMID 10969344. Retrieved 2012-03-29. Unknown parameter |month= ignored (help)
  25. ↑ Niederau C, Heintges T, Lange S, Goldmann G, Niederau CM, Mohr L, Häussinger D (1996). "Long-term follow-up of HBeAg-positive patients treated with interferon alfa for chronic hepatitis B". N. Engl. J. Med. 334 (22): 1422–7. doi:10.1056/NEJM199605303342202. PMID 8618580. Retrieved 2012-03-30. Unknown parameter |month= ignored (help)
  26. ↑ Yao FY, Terrault NA, Freise C, Maslow L, Bass NM (2001). "Lamivudine treatment is beneficial in patients with severely decompensated cirrhosis and actively replicating hepatitis B infection awaiting liver transplantation: a comparative study using a matched, untreated cohort". Hepatology. 34 (2): 411–6. doi:10.1053/jhep.2001.26512. PMID 11481627. Retrieved 2012-03-30. Unknown parameter |month= ignored (help)
  27. ↑ Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH (2006). "Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level". JAMA. 295 (1): 65–73. doi:10.1001/jama.295.1.65. PMID 16391218. Retrieved 2012-03-30. Unknown parameter |month= ignored (help)
  28. ↑ Chen G, Lin W, Shen F, Iloeje UH, London WT, Evans AA (2006). "Past HBV viral load as predictor of mortality and morbidity from HCC and chronic liver disease in a prospective study". Am. J. Gastroenterol. 101 (8): 1797–803. doi:10.1111/j.1572-0241.2006.00647.x. PMID 16817842. Retrieved 2012-03-30. Unknown parameter |month= ignored (help)
  29. ↑ Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ (2006). "Predicting cirrhosis risk based on the level of circulating hepatitis B viral load". Gastroenterology. 130 (3): 678–86. doi:10.1053/j.gastro.2005.11.016. PMID 16530509. Retrieved 2012-03-30. Unknown parameter |month= ignored (help)
  30. ↑ Liaw YF (2005). "The current management of HBV drug resistance". J. Clin. Virol. 34 Suppl 1: S143–6. PMID 16461216. Retrieved 2012-03-30. Unknown parameter |month= ignored (help)
  31. ↑ Liaw YF (2006). "Hepatitis B virus replication and liver disease progression: the impact of antiviral therapy". Antivir. Ther. (Lond.). 11 (6): 669–79. PMID 17310811. |access-date= requires |url= (help)
  32. ↑ Yuan HJ, Yuen MF, Ka-Ho Wong D, Sablon E, Lai CL (2005). "The relationship between HBV-DNA levels and cirrhosis-related complications in Chinese with chronic hepatitis B". J. Viral Hepat. 12 (4): 373–9. doi:10.1111/j.1365-2893.2005.00603.x. PMID 15985007. Retrieved 2012-03-30. Unknown parameter |month= ignored (help)
  33. ↑ Yuen MF, Yuan HJ, Wong DK, Yuen JC, Wong WM, Chan AO, Wong BC, Lai KC, Lai CL (2005). "Prognostic determinants for chronic hepatitis B in Asians: therapeutic implications". Gut. 54 (11): 1610–4. doi:10.1136/gut.2005.065136. PMC 1774768. PMID 15871997. Retrieved 2012-03-30. Unknown parameter |month= ignored (help)
  34. ↑ Keeffe EB, Zeuzem S, Koff RS, Dieterich DT, Esteban-Mur R, Gane EJ, Jacobson IM, Lim SG, Naoumov N, Marcellin P, Piratvisuth T, Zoulim F (2007). "Report of an international workshop: Roadmap for management of patients receiving oral therapy for chronic hepatitis B". Clin. Gastroenterol. Hepatol. 5 (8): 890–7. doi:10.1016/j.cgh.2007.05.004. PMID 17632041. Retrieved 2012-03-30. Unknown parameter |month= ignored (help)
  35. ↑ Keeffe EB, Dieterich DT, Han SH, Jacobson IM, Martin P, Schiff ER, Tobias H (2008). "A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2008 update". Clin. Gastroenterol. Hepatol. 6 (12): 1315–41, quiz 1286. doi:10.1016/j.cgh.2008.08.021. PMID 18845489. Retrieved 2012-03-30. Unknown parameter |month= ignored (help)
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