Chronic hepatitis B virus (CHB) infection is a serious problem that affects over 300 million people worldwide and is highly prevalent in the Asia- Pacific region. In the Philippines, an estimated 7.3 million Filipinos or 16.7% of adults are chronically infected with HBV, more than twice the average prevalence in the Western Pacific region.

In view of the above, the Hepatology Society of the Philippines (HSP) embarked on the development of consensus statements on the management of hepatitis B with the primary objectives of standardizing approach to management, empowering other physicians involved in the management of hepatitis B and advancing treatment subsidy by the Philippine Health Insurance Corporation (PhilHealth).

The local guidelines include screening and vaccination, general management, indications for assessment of fibrosis in those who did not meet treatment criteria, indications for treatment, on-treatment and post-treatment monitoring and duration of antiviral treatment. Recommendations on the management of antiviral drug resistance, management of special populations including patients with concurrent HIV or hepatitis C infection, women of child-bearing age (pregnancy and breastfeeding), patients with decompensated liver disease, patients receiving immunosuppressive medications or chemotherapy and patients in the setting of hepatocellular carcinoma are also included. However, the guidelines did not include management for patients with liver and other solid organ transplantation, patients on renal replacement therapy, and children.

The consensus statements will be amended accordingly as new therapies become available.

Keywords: Hepatitis B, guidelines, management

1. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of chronic hepatitis B virus infection. J Hepatol, 57:167-85, 2012.
2. Lok ASF, McMahon BJ. AASLD practice guideline update: Chronic hepatitis B: Update 2009. Hepatology, 50:1-36, 2009.
3. Wong SN, Ong JP, Labio ME, Cabahug OT, Daez ML, Valdellon EV, Sollano JD Jr, Arguillas MO. Hepatitis B infection among adults in the Philippines: A national seroprevalence study. World J Hepatol, 5:214-9, 2013.
4. Hwang EW, Cheung R. Global epidemiology of hepatitis B virus (HBV) infection. N A J Med Sci, 4:7-13, 2011.
5. National Institutes of Health. NIH consensus development conference statement on management of hepatitis B. NIH Consensus and State-of-the-Science Statements. 2008;25.
6. Clements CH, Baoping Y, Crouch A, Hipgrave D, Mansoor O, Nelson CB, Treleaven S, van Konkelenberg, Wiersma S. Progress in the control of hepatitis B infection in the Western Pacific Region. Vaccine, 24:1975-82, 2006.
7. Goldstein ST, Zhou F, Hadler SC, Bell BP, Mast EE, Margolis HS. A mathematical model to estimate global hepatitis B disease burden and vaccination impact. Int J Epidemiol, 34:1329-39, 2005.
8. Liaw YF, Leung N, Kao JH, Piratvisuth T, Chan HLK, Chien RN, Liu CJ, Gane E, Locarnini S, Lim SG, Han, KH, Amarapurkar D, Cooksley G, Jafri W, Mohamed R, Hou JL, Chuang WL, Lesmana LA, Sollano JD, Suh DH, Omata M. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update. Hepatol Int, 6:531-61, 2012.
9. McMahon BJ, Parkinson AJ, Helminiak C, Wainright RB, Bulkow L, Kellerman-Douglas A, Schoenberg S, Ritter D. Response to hepatitis B vaccine of persons positive for antibody to hepatitis B core antigen. Gastroenterology, 103:590-4, 1992.
10. Al-Mekhaizeem KA, Miriello M, Sherker AH. The frequency and significance of isolated hepati¬tis B core antibody and the suggested management of patients. CMAJ, 165:1063-4, 2001.
11. Almedia Neto C, Strauss E, Sabino EC, Sucupira MC, Chamone DA. Significance of isolated hepatitis B core antibody in blood from Sao Paulo. Rev Inst Med Trop Sao Paolo, 43:203-8, 2001.
12. Reiss G, Keeffe EB. Review article: hepatitis vaccination in patients with chronic liver disease. Aliment Pharmacol Ther, 19:715-27, 2004.
13. Chan H, Thompson A, Martinot-Peignoux M, Piratvisuth T, Cornberg M, Brunetto MR, Tillman HL, Kao JH, Jia JD, Wedemeyer H, Locarnini S, Janssen HL, Marcellin P. Hepatitis B surface antigen quantification: why and how to use it in 2011 – a core group report. J Hepatol, 55:1121-31, 2011.
14. Bruix J, Sherman M. American Association for the Study of Liver Diseases. AASLD Practice Guideline. Management of hepatocellular caricinoma: an update. Hepatology, 53:1020-2, 2011.
15. Omata M, Lesmana LA, Tateishi R, Chen PJ, Lin SM, Yoshida H, Kudo M, Lee JM, Choi BI, Poon RT, Shiina S, Cheng AL, Jia JD, Obi S, Han KH, Jafri W, Chow P, Lim SG, Chawla YK, Budihusodo U, Gani RA, Lesmana CR, Putranto TA, Liaw YF, Sarin SK. Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma. Hepatol Int, 4:439-74, 2010.
16. Belongia EA, Costa J, Gareen IF, Grem JL, Inadomi JM, Kern ER, McHugh JA, Peterson GM, Rein MF, Sorrell MF, Strader DB, Trotter HT. NIH Consensus development statement on management of hepatitis B. NIH Consens State Sci Statements, 25:1-29, 2008.
17. Wu CF, Yu MW, Lin CL, Liu CJ, Shih WL, Tsai KS, Chen CJ. Long-term tracking of hepatitis B viral load and the relationship with risk for hepatocellular carcinoma in men. Carcinogenesis, 29:106-12, 2008
18. Nguyen VT, Law MG, Dore GJ. Hepatitis B-related hepatocellular carcinoma: epidemiological characteristics and disease burden. J Viral Hepat, 16:453-63, 2009.
19. Keeffe EB. Hepatitis A and B superimposed on chronic liver disease: vaccine-preventable diseases. Trans Am Clin Climatol Assoc, 117:227-37, 2006.
20. Keeffe EB. Is hepatitis A more severe in patients with chronic hepatitis B and other chronic liver diseases? Am J Gastroenterol, 90:201-5, 1995.
21. Fiore AE, Wasley A, Bell BP. Prevention of hepatitis A through active or passive immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep, 55;1-23, 2006.
22. Akriviadis EA, Redeker AG. Fulminant hepatitis A in intravenous drug users with chronic liver disease. Ann Intern Med, 110:838-9, 1989.
23. Williams I, Bell B, Kaluba J, Shapiro C. Association between chronic liver disease and death from hepatitis A, United States, 1989-92 [Abstract no. A39]. IX Triennial International Symposium on Viral Hepatitis and Liver Disease. Rome, Italy, April 21-25, 1996.
24. Yuen MF, Yuan HJ, Wong DK, Yuen JC, Wong WM, Chan AO, Wong BC, Lai KC, Lai CL. Prognostic determinants for chronic hepatitis B in Asians: therapeutic implications. Gut, 54:1610-4, 2005.
25. Göbel T, Erhardt A, Herwig M, Poremba C, Baldus SE, Saqir A, Heinzel-Pleines U, Häussinger D. High prevalence of significant liver fibrosis and cirrhosis in chronic hepatitis B patients with normal ALT in central Europe. J Med Virol, 83:968-73, 2011.
26. Sporea I, Sirli R, Deleanu A, Popescu A, Cornianu M. Liver stiffness measurement by transient elastography in clinical practice. J Gastrointestin Liver Dis, 17:395-9, 2008.
27. Jung KS, Kims SU, Ahn SH, Park YN, Kim do Y, Park JY, Chon CY, Choi EH, Han KH. Risk assessment of hepatitis B virus-related hepatocellular carcinoma development using liver stiffness measurement (FibroScan). Hepatology, 53:885-94, 2011.
28. Cardoso AC, Carvalho-Filho RJ, Stern C, Dipumpo A, Giuily N, Ripault MP, Asselah T, Boyer N, Lada O, Castelnau C, Martinot-Peignoux M, Valla DC, Bedossa P, Marcellin P. Direct comparison of diagnostic performance of transient elastography in patients with chronic hepatitis B and chronic hepatitis C. Liver Int, 32:612-21, 2012.
29. Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH, REVEAL-HBV Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA, 295:65-73, 2006.
30. Degertekin B, Lok AS. Indications for therapy in hepatitis B. Hepatology, 49:S129-37, 2009.
31. Chang TT, Lai CL, Kew YS, Lee SS, Coelho HS, Carriho FJ, Poordad F, Halota W, Horsmans Y, Tsai N, Zhang H, Tenney DJ, Tamez R, Iloeje U. Entecavir treatment for up to 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B. Hepatology, 51:422-30, 2010.
32. Marcellin P, Gane E, Buti M, Afdhal N, Sievert W, Jacobson IM, Washington MK, Germanidis G, Flaherty JF, Schall RA, Bornstein JD, Kitrinos KM, Subramanian GM, McHutchinson JG, Heathcote EJ. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet, 381:468-75, 2013.
33. Dienstag JL, Goldin RD, Heathcote EJ, Hann HW, Woessner M, Stephenson SL, Gardner S, Gray DF, Schiff ER. Histological outcome during long-term lamivudine therapy. Gastroenterology, 124:105-17, 2003.
34. Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, Tao QM, Shue K, Keene ON, Dixon JS, Gray DF, Sabbat J, Cirrhosis Asian Lamivudine Multicentre Study Group. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Eng J Med, 351:1521-31, 2004.
35. Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, Marcellin P, Lim SG, Goodman Z, Ma J, Brosgart CL, Borroto-Esoda K, Arterburn S, Chuck SL; Adefovir Dipivoxil 438 Study Group. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years. Gastroenterology, 131:1743-51, 2006.
36. Marcellin P , Chang TT, Lim SG, Sievert W, Tong M, Arterburn S, Borroto-Esoda K, Frederick D, Rousseau F. Long-term efficacy and safety of adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. Hepatology, 48:750-8, 2008.
37. Andersson KL, Chung RT. Monitoring during and after antiviral therapy for hepatitis B. Hepatology, 49:S166-S73, 2009.
38. Gane EJ. The Roadmap concept: using early on-treatment virologic treatment responses to optimize long-term outcomes for patients with chronic hepatitis B. Hepatol Int, 2:304-7, 2008.
39. Bhattacharya D, Thiol CL. Review of hepatitis B therapeutics. Clin Infect Dis 2010;51:1201-8.
40. Keeffe EB, Dieterich DT, Han SH, Jacobson IM, Martin P, Schiff ER, Tobias H. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2008 update. Clin Gastroenterol Hepatol, 6:1315-41, 2008.
41. Seok JI, Lee DK, Lee CH, Park MS, Kim SY, Kim HS, Jo HY, Lee CH, Kim DS. Long-term therapy with clevudine for chronic hepatitis B can be associated with myopathy characterized by depletion of mitochondrial DNA. Hepatology, 49:2080-6, 2009.
42. Chaung KT, Ha NB, Trinh HN, Garcia RT, Nguyen HA, Nguyen KK, Garcia G, Ahmed A, Keeffe EB, Nguyen MH. J Clin Gastroenterol 2012;46:865-70, 2012.
43. Yeh CT, Hsu CW, Chen YC, Liaw YF. Withdrawal of lamivudine in HBeAg-positive chronic hepatitis B patients after achieving effective maintained virological suppression. J Clin Virol, 45:114-8, 2009.
44. Jin YJ, Kim KM, Yoo DJ, Shim JH, Lee HC, Chung YH, Lee YS, Suh DJ. Clinical course of chronic hepatitis B patients who were off-treated after lamivudine treatment: analysis of 138 consecutive patients. Virol J, 9:239, 2012.
45. Liu F, Wang L, Li XY, Liu YD, Wang JB, Zhang ZH, Wang YZ. Poor durability of lamivudine effectiveness despite stringent cessation criteria: a prospective clinical study in hepatitis B e antigen-negative chronic hepatitis B patients. J Gastroenterol Hepatol, 26:456-60, 2011.
46. Fung SK, Wong F, Hussain M, Lok AS. Sustained response after a 2-year course of lamivudine treatment of hepatitis B e antigen-negative chronic hepatitis B. J Viral Hepatol, 11:432-8, 2004.
47. Jeng WJ, Sheen IS, Chen YC, Hsu CW, Chien RN, Chu CM, Liaw YF. Off therapy durability in chronic hepatitis B e antigen negative patients treated with entecavir. Hepatology, 54:S1014A abst 1379, 2011.
48. Lin SM, Yu ML, Lee CM, Chien RN, Sheen IS, Chu CM, Liaw YF. Interferon therapy in HBeAg positive chronic hepatitis reduces progression to cirrhosis and hepatocellular carcinoma. J Hepatol, 46:45-52, 2007.
49. Piratvisuth T. Reviews for APASL guidelines: immunomodulator therapy of chronic hepatitis B. Hepatol Int, 2:140-6, 2008.
50. Piratvisuth T, Lau G, Chao YC, Jin R, Chutaputti A, Zhang QB, Tanwandee T, Button P, Popescu M. Sustained response to peginterferon alfa-2a (40kD) with or without lamivudine in Asian patients with HBeAg-positive and HBeAg-negative chronic hepatitis B. Hepatol Int, 2:102-10, 2008.
51. Liaw YF, Jia JD, Chan HL, Han KH, Tanwandee T, Chuang WL, Tan DM, Chen XY, Gane E, Piratvisuth T, Chen L, Xie Q, Sung JJ, Wat C, Bernaards C, Cui Y, Marcellin P. Shorter durations and lower doses of peginterferon alfa-2a are associated with inferior hepatitis B e antigen seroconversion rates in hepatitis B virus genotypes B or C. Hepatology, 54:1591-9, 2011.
52. Marcellin P, Lau GK, Bonino F, Farci P, Hadziyannis S, Jin R, Lu ZM, Piratvisuth T, Germanidis G, Yurdaydin C, Diago M, Gurel S, Lai MY, Button P, Pluck N; Peginterferon Alfa-2a HBeAg-Negative Chronic Hepatitis B Study Group. N Engl J Med, 351:1206-17, 2004.
53. Papadopoulos VP, Chrysagis DN, Protopapas AN, Goulis IG, Dimitriadis GT, Mimidis KP. Peginterferon alfa-2b as monotherapy or in combination with lamivudine in patients with HBeAg-negative chronic hepatitis B: a randomised study. Med Sci Monit, 15:CR56-61, 2009.
54. Lampertico P, Del Ninno E, Viganò M, Romeo R, Donato MF, Sablon E, Morabito A, Colombo M. Long-term suppression of hepatitis B e antigen-negative chronic hepatitis B by 24-month interferon therapy. Hepatology,37:756-3, 2003.
55. Gish RG, Lau DT, Schmid P, Perrillo R. A pilot study of extended duration peginterferon alfa-2a for patients with hepatitis B e antigen-negative chronic hepatitis B. Am J Gastroenterol, 102:2718-23, 2007.
56. Lampertico P, Viganò M, Di Costanzo GG, Sagnelli E, Fasano M, Di Marco V, Boninsegna S, Farci P, Fargion S, Giuberti T, Iannacone C, Regep L, Massetto B, Facchetti F, Colombo M; PegBeLiver Study Group. Randomised study comparing 48 and 96 weeks peginterferon α-2a therapy in genotype D HBeAg-negative chronic hepatitis B. Gut, 62:290-8, 2013.
57. Piratvisuth T, Marcellin P, Popescu M, Kapprell HP, Rothe V, Lu ZM. Hepatitis B surface antigen: association with sustained response to peginterferon alfa-2a in hepatitis B e antigen-positive patients. Hepatol Int, doi:10.1007/s12072- 011-9279-6, 2011.
58. Sonneveld MJ, Rijckborst V, Boucher CA, Hansen BE, Janssen HL. Prediction of sustained response to peginterferon alfa-2b for hepatitis B e antigen-positive chronic hepatitis B using on-treat¬ment hepatitis B surface antigen decline. Hepatology, 52:1251-7, 2010.
59. Rijckborst V, Hansen BE, Cakaloglu Y, Ferenci P, Tabak F, Akdogan M, Simon K, Akarca US, Flisiak R, Verhey E, Van Vuuren AJ, Boucher CA, ter Borg MJ, Janssen HL. Early on-treatment prediction of response to peginterferon  alfa-2a for HBeAg-negative chronic hepatitis B using HBsAg and HBV DNA levels. Hepatology, 52:454-61, 2010.
60. Rijckborst V, Hansen BE, Ferenci P, Brunetto MR, Tabak F, Cakaloglu Y, Lanza AG, Messina V, Iannacone C, Massetto B, Regep L, Colombo M, Janssen HL, Lampertico P. Validation of a stopping rule at week 12 using HBsAg and HBV DNA for HBeAg-negative patients treated with peginterferon alfa-2a. J Hepatol, 56:1006-11, 2012.
61. Lee HW, Lee HJ, Hwang JS, Sohn JH, Jang JY, Han KJ, Park JY, Kim do Y, Ahn SH, Paik YH, Lee CK, Lee KS, Chon CY, Han KH. Lamivudine maintenance beyond once year after HBeAg seroconversion is a major factor for sustained virologic response in HBeAg-postive chronic hepatitis B. Hepatology, 51:415-21, 2010.
62. Wu IC, Shiffman ML, Tong MJ, Marcellin P, Mondou E, Frederick D, Snow-Lampart A, Sorbel J, Rousseau F, Chang TT. Sustained hepatitis B e antigen seroconversion in patients with chronic hepatitis B after adefovir dipivoxil treatment: analysis of precore and basal core promoter mutants. Clin Infect Dis, 47:1305-11, 2008.
63. Shouval D, Lai CL, Chang TT, Cheinquer H, Martin P, Carosi G, Han S, Kaymakoglu S, Tamez R, Yang J, Tenney D, Brett-Smith H. Relapse of hepatitis B in HBeAg-negative chronic hepatitis B patients who discontinued successful entecavir treatment: the case for continuous antiviral therapy. J Hepatol, 50:289-95, 2009.
64. Santantonio T, Mazzola M, Iacovazzi T, Miglietta A, Guastadisegni A, Pastore G. Long-term follow-up of patients with anti-HBe/HBV DNA-positive chronic hepatitis B treated for 12 months with lamivudine. J Hepatol, 32:300-6, 2000.
65. Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, Marcellin P, Lim SG, Goodman Z, Ma J, Arterburn S, Xiong S, Currie G, Brosgart CL; Adefovir Dipivoxil438 Study Group. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B. N Engl J Med, 352:2673-81, 2005.
66. Ha M, Zhang G, Diao S, Diao S, Lin M, Sun L, She H, Kuan C, Shen L, Huang C, Shen W, Huang Z. A prospective clinical study in hepatitis B e antigen-negative chronic hepatitis B patients with stringent cessation criteria for adefovir. Arch Virol, 157:285-90, 2012.
67. Sheen E, Trinh HN, Nguyen TT, Do ST, Tran P, Nguyen HA, Nguyen KK, Garcia RT, Nguyen MH. The efficacy of entecavir therapy in chronic hepatitis B patients with suboptimal response to adevofir. Aliment Pharmacol Ther, 34:767-74, 2011.
68. Antiretroviral Pregnancy Registry Steering Committee. Antiretroviral Pregnancy Registry International Interim Report for January 1, 1989-July 31, 2011. Wilmington, NC: Registry Coordinating Center;2011.
69. Ranger-Rogez S, Denis F. Hepatitis B mother-to-child transmission. Expert Rev Infect Ther, 2:133-45, 2004.
70. del Canho R, Grosheide PM, Mazel JA, Heijtnik RA, Hop WC, Geralds LJ, de Gast GC, Fetter WP, Zwijnberg J, Schalm SW. Ten-year hepatitis B vaccination program, The Netherlands, 1982-1999: protective efficacy and long-term immunogenicity. Vaccine, 15:1624-30, 1997.
71. Buchanan C, Tran TT. Management of chronic hepatitis B in pregnancy. Clin Liver Dis, 14:495-504, 2010.
72. Pan CQ, Duan ZP, Bhamidimarri KR, Zou HB, Liang XF, Li J, Tong MJ. An algorithm for risk assessment and intervention of mother to child transmission of hepatitis B virus. Clin Gastroenterol, 10:452-9, 2012.
73. Wiseman E, Fraser MA, Holden S, Glass A, Kidson BL, Heron LG, Maley MW, Ayres A, Locarnini SA, Levy MT. Perinatal transmission of hepatitis B virus: an Australian experience. Med J Aust, 190:489-92, 2009.
74. Han GR, Cao MK, Zhao W, Jiang HX, Wang CM, Bai SF, Yue X, Wang GJ, Tang X, Fang ZX. A prospective and open-label study for the efficacy and safety of telbivudine in pregnancy for the prevention of perinatal transmission of hepatitis B virus infection. J Hepatol, 55:1215-21, 2011.
75. Deng M, Zhou X, Gao S, Yang SG, Wang B, Chen HZ, Ruan B. The effects of telbivudine in late pregnancy to prevent intrauterine transmission of the hepatitis B virus: a systematic review and meta-analysis. Virol J, 9:185, 2012.
76. van Zonneveld M, van Nunen AB, Niesters HG, de Man RA, Schalm SW, Janssen HL. Lamivudine treatment during pregnancy to prevent perinatal transmission of hepatitis B virus infection. J Viral Hepatol, 10:294-7, 2003.
77. Xu WM, Cui YT, Wang L, Yang H, Liang ZQ, Li XM, Zhang SL, Quiao FY, Campbell F, Chang CN, Gardner S, Atkins M. Lamivudine in late pregnancy to prevent perinatal transmission of hepatitis B virus infection: a multicentre, randomized, double-blind, placebo-controlled study. J Viral Hepatol, 16:94-103, 2009.
78. Petrova M, Kamburov V. Breastfeeding and chronic HBV infection: clinical and social implications. World J Gastroenterol, 16:5042-6, 2010.
79. Wang JS, Zhu QR, Wang XH. Breastfeeding does not pose any additional risk of immunoprophylaxis failure on infants of HBV carrier mothers. Int J Clin Pract, 57:100-2, 2003.
80. Hill JB, Sheffield JS, Kim MJ, Alexander JM, Sercely B, Wendel GD. Risk of hepatitis B transmission in breast-fed infants of chronic hepatitis B carriers. Obstet Gynecol, 99:1049-52, 2002.
81. Benaboud S, Pruvost A, Coffie PA, Ekouevi DK, Urien S, Arrive E, Blanche S, Theodoro F, Avit D, Dabis F, Treluyer JM, Hirt D. Concentrations of tenofovir and emtricitabine in breast milk of HIV-1-infected women in Abdidjan, Cote d’Ivoire, in the ANRS 12109 TEmAA Study. Step 2. Antimicrob Agents Chemother, 55:1315-7, 2011.
82. Chu CM, Yeh CT, Liaw YF. Fulminant hepatic failure in acute hepatitis C: increased risk of chronic carriers of hepatitis B virus. Gut, 45:613-7, 1999.
83. Chu CM. Natural history of chronic hepatitis B virus infection in adults with emphasis on the occurrence of cirrhosis and hepatocellular carcinoma. J Gastroenterol Hepatol, 15(Suppl):E25-30, 2000.
84. Chuang CS, Tung SY, Lee IL, Shen CH, Wei KL, Chang TS, Wu CS. Clinical features and outcome of chronic viral hepatitis with acute exacerbation in patients with concurrent infectious hepatitis B and C virus. Dig Dis Sci, 53:511-6, 2008.
85. Perumalswami PB, Bini EJ. Epidemiology, natural history, and treatment of hepatitis B virus and hepatitis C virus coinfection. Minerva Gastroenterol Dietol, 52:145-55, 2006.
86. Chiaramonte M, Stroffolini T, Vian A, Stazi MA, Floreani A, Lorenzoni U, Lobello S, Farinati F, Naccarato R. Rate of incidence of HBV/HCV coinfection hepato¬cellular carcinoma in patients with compensated viral cirrhosis. Cancer, 85:2132-7, 1999.
87. Donato F, Boffetta P, Puoti M. A meta-analysis of epidemiological studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma. Int J Cancer, 75:347-54, 1998.
88. Chen LW, Chien RN, Yen CL, Chang JJ, Liu CJ, Lin CL. Therapeutic effect of pegylated interferon plus ribavirin in chronic hepatitis C patients with occult hepatitis B virus dual infection. J Gastroenterol Hepatol, 25:259-63, 2010.
89. Chen SW, Lee TS, Hu CC, Chang LC, Chien RN. Simultaneously acute hepatitis B and C virus coinfection and subsequent chronic hepatitis C. Scand J Infect Dis, 39:351-4, 2007.
90. Yeh ML, Hung CH, Huang JF, Liu CJ, Lee CM, Dai CY, Wang JH, Lin ZY, Lu SN, Hu TH, Yu ML, Kao JH, Chuang WL, Chen PJ, Chen DS. Long-term effect of inter¬feron plus ribavirin on hepatitis B surface antigen seroclearance in patients dually infected with hepatitis B and C viruses. PLoS ONE, 6:e20752, 2011.
91. Potthoff A, Manns M, Wedemever H. Treatment of HBV/ HCV coinfection. Expert Opin Pharmacother, 11:919-28, 2010.
92. Chu CJ, Lee SD. Hepatitis B virus/hepatitis C virus coinfection: epidemiology, clinical features, viral interactions and treatment. J Gastroenterol Hepatol, 23:512-20, 2008.
93. World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. Available at: http://www.who.int/iris/ bitstream/10665/85321/1/9789241505727_eng.pdf. Accessed on August 22, 2013.
94. Department of Health Revised Antiretroviral Therapy Guideline 2014.
95. McMahon MA, Jilek BL, Brennan TP, Shen L, Zhou Y, Wind-Rotolo M, Xing S, Bhat S, Hale B, Hegarty R, Chong CR, Liu JO, Siliciano RF, Thio CL. The HBV drug entecavir – effects on HIV-1 replication and resistance. N Engl J Med, 356:2614-21, 2007.
96. Soriano V, Tuma P, Vispo E, Labarga P, Fernandez JV, Medrano J, Barreiro P. Hepatitis B in HIV patients: what is the current treatment and what are the challenges? J HIV Ther, 14:13-8, 2009.
97. Kouanfack C, Aghokeng AF, Mondain AM, Bourgeois A, Kenfack A, Mpoudi-Ngole E, Ducos J, Delaporte E, Laurent C. Lamivudine-resistant HBV infection in HIV-positive patients receiving antiretroviral therapy in a public routine clinic in Cameroon. Antivir Ther, 17:321-6, 2012.
98. Lim SG. A double-blind placebo-controlled study of emtricitabine in chronic hepatitis B. Arch Int Med, 166:49- 56, 2006.
99. Ayoub WS, Keeffe EB. Review article: current antiviral therapy of chronic hepatitis B. Aliment Pharmacol Ther, 28:167-77, 2008.
100. Lok AS, McMahon BJ. Chronic hepatitis B: Update 2009. Hepatology, 5:661-2, 2009.
101. de Jongh FE, Janssen HL, de Man RA, Hop WC, Schalm SW, van Blankenstein M. Survival and prognostic indicators in hepatitis B surface antigen-positive cirrhosis of the liver. Gastroenterology, 103:1630-5, 1992.
102. Peng CY, Chien RN, Llaw YF. Hepatitis B virus-related decompensated liver cirrhosis: benefits of antiviral therapy. J Hepatol, 57:442-50, 2012.
103. Shim JH, Lee HC, Kim KM, Lim YS, Chung YH, Lee YS, Suh DJ. Efficacy of entecavir in treatment-naive patients with hepatitis B virus-related decompensated cirrhosis. J Hepatol, 52:176-82, 2010.
104. Liaw YF, Raptopoulou-Gigi M, Cheinquer H, Sarin SK, Tanwandee T, Leung N, Peng CY, Myers RP, Brown RS Jr, Jeffers L, Bialkowska J, Tang S, Beebe S, Cooney E. Efficacy and safety of entecavir versus adefovir in chronic hepatitis B patients with hepatic decompensation: a randomized, open-label study. Hepatology, 54:91-100, 2011.
105. Liaw YF, Sheen IS, Lee CM, Akarca US, Papatheodoridis GV, Suet-Hing Wong F, Chang TT, Horban A, Wang C, Kwan P, Buti M, Prieto M, Berg T, Kitrinos K, Peschell K, Mondou E, Frederick D, Rousseau F, Schiff ER. Tenofovir disoproxil fumarate (TDF), emtricitabine/ TDF, and entecavir in patients with decompensated chronic hepatitis B liver disease. Hepatology, 53:62-72, 2011.
106. Zoulim F, Loucarnini S. Hepatitis B resistance to nucelos(t) ide analogues. Gastroenterology, 137:1593-1608.e1-2, 2009.
107. Ghany MG, Doo EC. Antiviral resistance and hepatitis B therapy. Hepatology, 49(5 Suppl):S174-84, 2009.
108. Lampertico P, Viganò M, Manenti E, Iavarone M, Sablon E, Colombo M. Low resistance to adefovir combined with lamivudine: a 3-year study of 145 lamivuidine-resistant hepatitis B patients. Gastroenterology, 133:1441-51, 2007.
109. Rapti I, Dimou E, Mitsoula P, Hadzjyannis SJ. Adding-on versus switching-to adefovir therapy in lamivudine-resistant HBeAg-negative chronic hepatitis B. Hepatology, 45:307-13, 2007.
110. Sheng YJ, Liu JY, Tong SW, Hu HD, Zhang DZ, Hu P, Ren H. Lamivudine plus adefovir combination therapy versus entecavir monotherapy for lamivudine-resistant chronic hepatitis B: a systematic review and meta-analysis. Virol J, 8:393, 2011.
111. van Bömmel F, de Man RA, Wedemeyer H, Deterding K, Petersen J, Buggisch P, Erhardt A, Hüppe D, Stein K, Trojan J, Sarrazin C, Böcher WO, Spengler U, Wasmuth HE, Reinders JG, Möller B, Rhode P, Feucht HH, Wiedenmann B, Berg T. Long-term efficacy of tenofovir monotherapy for hepatitis B virus-monoinfected patients after failure of nucleoside/nucleotide analogues. Hepatology, 51:73-80, 2010.
112. Sun J, Hou JL, Xie Q, Li XH, Zhang JM, Wang YM, Wang H, Lai JY, Chen SJ, Jia JD, Sheng JF, Chan HL, Wang JF, Li MK, Jiang M, Popescu M, Sung JJ. Randomised clinical trial: efficacy of peginterferon alfa-2a in HBeAg-positive chronic hepatitis B patients with lamivuidine resistance. Aliment Pharmacol Ther, 34:424-31, 2011.
113. Loomba R, Rowley A, Wesley R, Liang TJ, Hoofnagle JH, Pucino F, Csako G. Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy. Ann Intern Med, 148:519-28, 2008.
114. Katz LH, Fraser A, Gafter-Gvili A, Leibovici L, Tur- Kaspa R. Lamivudine prevents reactivation of hepatitis B and reduces mortality in immunosuppressed patients: systematic review and meta-analysis. J Viral Hepat, 15:89-102, 2008.
115. Hoofnagle JH. Reactivation of hepatitis B. Hepatology, 49:S156-65, 2009.
116. Czuczman MS. CHOP plus rituximab chemoimmunotherapy of indolent B-cell lymphoma. Semin Oncol, 26(Suppl 14):88- 96, 1999.
117. Skrabs C, Muller C, Agis H, Mannhalter C, Jäger U. Treatment of HBV-carrying lymphoma patients with Rituximab and CHOP: a diagnostic and therapeutic challenge. Leukemia, 16:1884-6, 2002.
118. Tsutsumi Y, Tanaka J, Kawamura T, Miura T, Kanamori H, Obara S, Asaka M, Imamura M, Masauzi N. Possible efficacy of lamivudine treatment to prevent hepatitis B virus reactivation due to rituximab therapy in a patient with non-Hodgkin’s lymphoma. Ann Hematol, 83:58-60, 2004.
119. Dervite I, Hober D, Morel P. Acute hepatitis B in a patient with antibodies to hepatitis B surface antigen who was receiving rituximab. N Engl J Med, 344:68-9, 2001.
120. Westhoff TH, Jochimsen F, Schmittel A, Stoffler-Meilicke M, Schafer JH, Zidek W, Gerlich WH, Thiel E. Fatal hepatitis B virus reactivation by an escape mutant following rituximab therapy. Blood, 102:1930, 2003.
121. Sarrecchia C, Cappelli A, Aiello P. HBV reactivation with a fatal fulminating hepatitis during rituximab treatment in a subjective negative HBsAg and positive for HBsAb and HBcAb. J Infect Chemother, 11:189-91, 2005.
122. Lundin J, Kimby E, Björkholm M, Broliden PA, Celsing F, Hjalmar V, Mollgard L, Rebello P, Hale G, Waldmann H, Mellstedt H, Osterborg A. Phase II trial of subcutaneous anti-CD52 monoclonal antibody alemtuzumab (Campath-1H) as first-line treatment for patients with B-cell chronic lymphocytic leukemia (B-CLL). Blood, 100:768-73, 2002.  
123. Iannitto E, Minardi V, Calvaruso G, Mule A, Ammatuna E, Di Trapani R, Ferraro D, Abbadessa V, Craxi A, Di Stefano R. Hepatitis B virus reactivation and alemtuzumab therapy. Eur J Haematol, 74:254-8, 2005.
124. Liu CJ, Chen PJ, Chen DS, Kao JH. Hepatitis B virus reactivation in patients receiving cancer chemotherapy: natural history, pathogenesis, and management. Hepatol Int, doi:10.1007/s12072-011-9279-6, 2011.
125. Hui CK, Cheung WW, Zhang HY, Au WY, Yueng YH, Leung AY, Leung N, Luk JM, Lie AK, Kwong YL, Liang R, Lau GK. Kinetics and risk of de novo hepatitis B infection in HBsAg-negative patients undergoing cytotoxic chemotherapy. Gastroenterology, 131:59-68, 2006.
126. Kohrt HE, Ouang DL, Keeffe EB. Systemic review: lamivudine prophylaxis for chemotherapy-induced reactivation of chronic hepatitis virus infection. Aliment Pharmacol Ther, 24:1003-16, 2006.
127. Jang WJ, Choi JY, Bae SH, Yoon SK, Chang UI, Kim CW, Cho SH, Han JY, Lee YS. A randomized controlled study of preemptive lamivudine in patients receiving transarterial chemo-lipiodolization. Hepatology, 43:233-40, 2006.
128. Huang L, Li J, Lau WY, Yan J, Zhou F, Liu C, Zhang X, Shen J, Wu M, Yan Y. Perioperative reactivation of hepatitis B virus replication in patients undergoing partial hepatectomy for hepatocellular carcinoma. J Gastroenterol Hepatol, 27:158-64, 2012.
129. Huang L, Li J, Lau WY, Zhou WP, Shen F, Pan ZY, Fu SY, Wu MC. Posthepatectomy HBV reactivation in hepatitis B-related hepatocellular carcinoma influences postoperative survival in patients with preoperative low HBV-DNA levels. Ann Surg, 257:490-505, 2013.
130. Huang L, Li J, Yan J, Sun J, Zhang X, Wu M, Yan Y. Antiviral therapy decreases viral reactivation in patients with hepatitis B virus-related hepatocellular carcinoma undergoing hepatectomy: a randomized controlled trial. J Viral Hepat, 20:336-42, 2013.
131. Tassopoulos NC, Papaevangelou SG, Sjogren MH, Roumeliotou-Karayannis A, Gerin JL, Purcell RH. Natural history of acute hepatitis B surface antigen-positive hepatitis in Greek adults. Gastroenterology, 92:1844-50, 1987.
132. Tillman HL, Zachou K, Dalekos GN. Management of severe acute to fulminant hep-atitis B: to treat or not to treat or when to treat? Liver Int, 32:544-53, 2012.
133. Tillman HL, Hadem J, Leifeld L, Zachou K, Canbay A, Eisenbach C, Graziadei I, Encke J, Schmidt H, Vogel W, Schneider A, Spengler U, Gerken G, Dalekos GN, Wedemeyer H, Manns MP. Safety and efficacy of lamivudine in patients with severe acute or fulminant hepatitis B, a multicenter experience. J Viral Hepat, 13:256-63, 2006.
134. Schmilovitz-Weiss H, Ben-Ari Z, Sikuler E, Zuckerman E, Sbeit W, Ackerman Z, Safadi R, Lurie Y, Rosner G, Tur-Kaspa R, Reshef R. Lamivudine treatment for acute severe hepatitis B: a pilot study. Liver Int, 24:547-51, 2004.
135. Kumar M, Satapathy S, Monga R, Das K, Hissar S, Pande C, Sharma BC, Sarin SK. A randomized controlled trial of lamivudine to treat acute hepatitis B. Hepatology, 45:97-101, 2007.
136. Guyatt, GH, Oxman AD, Vist G, Kunz R, Falck- Ytter, Y, Alonso-Coello P, Schunemann, HJ, for the GRADE Working Group. Rating Quality of evidence and strength of recommendations GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336:924-926.