Hepatitis B reactivation during or after direct acting antiviral therapy – implication for susceptible individuals

References

• (FAERS) TFaDAAERS. FDA Drug Safety Communication: FDA warns about risk of hepatitis B reactivating in some patients treated with direct-acting antivirals for hepatitis C; [updated 2016 Oct; cited 2017 Feb 18]. Available from: https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/ucm082193.html
   Google Scholar
• Balagopal A, Thio CL. Editorial commentary: another call to cure Hepatitis B. Clin Infect Dis. 2015;61:1307–1309.
   PubMed Web of Science ®Google Scholar
• Collins JM, Raphael KL, Terry C, et al. Hepatitis B virus reactivation during successful treatment of Hepatitis C virus with sofosbuvir and simeprevir. Clin Infect Dis. 2015;61:1304–1306.
   PubMed Web of Science ®Google Scholar
• De Monte A, Courjon J, Anty R, et al. Direct-acting antiviral treatment in adults infected with hepatitis C virus: reactivation of hepatitis B virus coinfection as a further challenge. J Clin Virol. 2016;78:27–30.
   PubMed Web of Science ®Google Scholar
• Ende AR, Kim NH, Yeh MM, et al. Fulminant hepatitis B reactivation leading to liver transplantation in a patient with chronic hepatitis C treated with simeprevir and sofosbuvir: a case report. J Med Case Rep. 2015;9:164.
   PubMedGoogle Scholar
• Wang C, Ji D, Chen J, et al. Hepatitis due to reactivation of Hepatitis B virus in endemic areas among patients with Hepatitis C treated with direct-acting antiviral agents. Clin Gastroenterol Hepatol. 2017;15:132–136.
   PubMed Web of Science ®Google Scholar
• Takayama H, Sato T, Ikeda F, et al. Reactivation of hepatitis B virus during interferon-free therapy with daclatasvir and asunaprevir in patient with hepatitis B virus/hepatitis C virus co-infection. Hepatol Res. 2016;46:489–491.
   PubMed Web of Science ®Google Scholar
• Kimura H, Ohkawa K, Sakakibara M, et al. Sustained hepatitis C virus RNA clearance accompanied by elevation of hepatitis B virus DNA after short-term peginterferon-α, ribavirin and simeprevir therapy in a chronic hepatitis patient having dual infection with hepatitis B and C viruses. Kanzo. 2015;56:422–427.
   Google Scholar
• Choo QL, Kuo G, Weiner AJ, et al. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 1989;244:359–362.
   PubMed Web of Science ®Google Scholar
• Ogata N, Alter HJ, Miller RH, et al. Nucleotide sequence and mutation rate of the H strain of hepatitis C virus. Proc Natl Acad Sci U S A. 1991;88:3392–3396.
   PubMed Web of Science ®Google Scholar
• Steinhauer DA, Domingo E, Holland JJ. Lack of evidence for proofreading mechanisms associated with an RNA virus polymerase. Gene. 1992;122:281–288.
   PubMed Web of Science ®Google Scholar
• Messina JP, Humphreys I, Flaxman A, et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology. 2015;61:77–87.
   PubMed Web of Science ®Google Scholar
• Gidding HF, Topp L, Middleton M, et al. The epidemiology of hepatitis C in Australia: notifications, treatment uptake and liver transplantations, 1997-2006. J Gastroenterol Hepatol. 2009;24:1648–1654.
   PubMed Web of Science ®Google Scholar
• Seeger C, Mason WS. Hepatitis B virus biology. Microbiol Mol Biol Rev. 2000;64:51–68.
   PubMed Web of Science ®Google Scholar
• Yen TS. Hepadnaviral X protein: reviewof recent progress. J Biomed Sci. 1996;3:20–30.
   PubMedGoogle Scholar
• Yan H, Zhong G, Xu G, et al. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. Elife. 2012;1:e00049.
   PubMed Web of Science ®Google Scholar
• Newbold JE, Xin H, Tencza M, et al. The covalently closed duplex form of the hepadnavirus genome exists in situ as a heterogeneous population of viral minichromosomes. J Virol. 1995;69:3350–3357.
   PubMed Web of Science ®Google Scholar
• Micallef JM, Kaldor JM, Dore GJ. Spontaneous viral clearance following acute hepatitis C infection: a systematic review of longitudinal studies. J Viral Hepat. 2006;13:34–41.
   PubMed Web of Science ®Google Scholar
• Averhoff FM, Glass N, Holtzman D. Global burden of hepatitis C: considerations for healthcare providers in the United States. Clin Infect Dis. 2012;55(Suppl 1):S10–15.
   PubMed Web of Science ®Google Scholar
• Schweitzer A, Horn J, Mikolajczyk RT, et al. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015;386:1546–1555.
   PubMed Web of Science ®Google Scholar
• Stevens CE, Beasley RP, Tsui J, et al. Vertical transmission of hepatitis B antigen in Taiwan. N Engl J Med. 1975;292:771–774.
   PubMed Web of Science ®Google Scholar
• Wasley A, Grytdal S, Gallagher K. Centers for Disease C, Prevention. Surveillance for acute viral hepatitis–United States, 2006. MMWR Surveill Summ. 2008;57:1–24.
   PubMedGoogle Scholar
• Tassopoulos NC, Papaevangelou GJ, Sjogren MH, et al. Natural history of acute hepatitis B surface antigen-positive hepatitis in Greek adults. Gastroenterology. 1987;92:1844–1850.
   PubMed Web of Science ®Google Scholar
• Mohd Hanafiah K, Groeger J, Flaxman AD, et al. Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology. 2013;57:1333–1342.
   PubMed Web of Science ®Google Scholar
• Frank C, Mohamed MK, Strickland GT, et al. The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt. Lancet. 2000;355:887–891.
   PubMed Web of Science ®Google Scholar
• Tyson GL, Kramer JR, Duan Z, et al. Prevalence and predictors of hepatitis B virus coinfection in a United States cohort of hepatitis C virus-infected patients. Hepatology. 2013;58:538–545.
   PubMed Web of Science ®Google Scholar
• Caccamo G, Saffioti F, Raimondo G. Hepatitis B virus and hepatitis C virus dual infection. World J Gastroenterol. 2014;20:14559–14567.
   PubMed Web of Science ®Google Scholar
• Mekky MA, Nasr AM, Saleh MA, et al. Virologic and histologic characterisation of dual hepatitis B and C co-infection in Egyptian patients. Arab J Gastroenterol. 2013;14:143–147.
   PubMed Web of Science ®Google Scholar
• Senturk H, Tahan V, Canbakan B, et al. Chronic hepatitis C responds poorly to combination therapy in chronic hepatis B carriers. Neth J Med. 2008;66:191–195.
   PubMed Web of Science ®Google Scholar
• Yan LB, Rao HY, Ma YJ, et al. Hepatitis B virus infection in Chinese patients with hepatitis C virus infection: prevalence, clinical characteristics, viral interactions and host genotypes: a nationwide cross-sectional study. BMJ Open. 2016;6:e012016.
   PubMed Web of Science ®Google Scholar
• Pramoolsinsap C, Sirikulchayanonta V, Busakorn W, et al. Coinfections with hepatitis g and/or c virus in hepatitis B-related chronic liver disease. Southeast Asian J Trop Med Public Health. 1999;30:741–749.
   PubMedGoogle Scholar
• Xess A, Kumar M, Minz S, et al. Prevalence of hepatitis B and hepatitis C virus coinfection in chronic liver disease. Indian J Pathol Microbiol. 2001;44:253–255.
   PubMedGoogle Scholar
• Fong TL, Di Bisceglie AM, Waggoner JG, et al. The significance of antibody to hepatitis C virus in patients with chronic hepatitis B. Hepatology. 1991;14:64–67.
   PubMed Web of Science ®Google Scholar
• Liaw YF, Chu CM, Chang-Chien CS, et al. Simultaneous acute infections with hepatitis non-A, non-B, and B viruses. Dig Dis Sci. 1982;27:762–764.
   PubMed Web of Science ®Google Scholar
• Baginski I, Chemin I, Hantz O, et al. Transmission of serologically silent hepatitis B virus along with hepatitis C virus in two cases of posttransfusion hepatitis. Transfusion. 1992;32:215–220.
   PubMed Web of Science ®Google Scholar
• Alberti A, Pontisso P, Chemello L, et al. The interaction between hepatitis B virus and hepatitis C virus in acute and chronic liver disease. J Hepatol. 1995;22:38–41.
   PubMed Web of Science ®Google Scholar
• Mimms LT, Mosley JW, Hollinger FB, et al. Effect of concurrent acute infection with hepatitis C virus on acute hepatitis B virus infection. Bmj. 1993;307:1095–1097.
   PubMed Web of Science ®Google Scholar
• Liaw YF, Chen YC, Sheen IS, et al. Impact of acute hepatitis C virus superinfection in patients with chronic hepatitis B virus infection. Gastroenterology. 2004;126:1024–1029.
   PubMed Web of Science ®Google Scholar
• Liaw YF. Hepatitis C virus superinfection in patients with chronic hepatitis B virus infection. J Gastroenterol. 2002;37(Suppl 13):65–68.
   PubMed Web of Science ®Google Scholar
• Wu JC, Chen CL, Hou MC, et al. Multiple viral infection as the most common cause of fulminant and subfulminant viral hepatitis in an area endemic for hepatitis B: application and limitations of the polymerase chain reaction. Hepatology. 1994;19:836–840.
   PubMed Web of Science ®Google Scholar
• Chu CM, Sheen IS, Liaw YF. The role of hepatitis C virus in fulminant viral hepatitis in an area with endemic hepatitis A and B. Gastroenterology. 1994;107:189–195.
   PubMed Web of Science ®Google Scholar
• Chu CM, Yeh CT, Liaw YF. Fulminant hepatic failure in acute hepatitis C: increased risk in chronic carriers of hepatitis B virus. Gut. 1999;45:613–617.
   PubMed Web of Science ®Google Scholar
• Liaw YF, Yeh CT, Tsai SL. Impact of acute hepatitis B virus superinfection on chronic hepatitis C virus infection. Am J Gastroenterol. 2000;95:2978–2980.
   PubMed Web of Science ®Google Scholar
• Sagnelli E, Coppola N, Messina V, et al. HBV superinfection in hepatitis C virus chronic carriers, viral interaction, and clinical course. Hepatology. 2002;36:1285–1291.
   PubMed Web of Science ®Google Scholar
• Sagnelli E, Pasquale G, Coppola N, et al. Influence of chronic coinfection with hepatitis B and C virus on liver histology. Infection. 2004;32:144–148.
   PubMed Web of Science ®Google Scholar
• Cacciola I, Pollicino T, Squadrito G, et al. Occult hepatitis B virus infection in patients with chronic hepatitis C liver disease. N Engl J Med. 1999;341:22–26.
   PubMed Web of Science ®Google Scholar
• Fukuda R, Ishimura N, Hamamoto S, et al. Co-infection by serologically-silent hepatitis B virus may contribute to poor interferon response in patients with chronic hepatitis C by down-regulation of type-I interferon receptor gene expression in the liver. J Med Virol. 2001;63:220–227.
   PubMed Web of Science ®Google Scholar
• Paterlini P, Driss F, Nalpas B, et al. Persistence of hepatitis B and hepatitis C viral genomes in primary liver cancers from HBsAg-negative patients: a study of a low-endemic area. Hepatology. 1993;17:20–29.
   PubMed Web of Science ®Google Scholar
• De Maria N, Colantoni A, Friedlander L, et al. The impact of previous HBV infection on the course of chronic hepatitis C. Am J Gastroenterol. 2000;95:3529–3536.
   PubMed Web of Science ®Google Scholar
• Pollicino T, Squadrito G, Cerenzia G, et al. Hepatitis B virus maintains its pro-oncogenic properties in the case of occult HBV infection. Gastroenterology. 2004;126:102–110.
   PubMed Web of Science ®Google Scholar
• Takeuchi O, Akira S. Innate immunity to virus infection. Immunol Rev. 2009;227:75–86.
   PubMed Web of Science ®Google Scholar
• Foy E, Li K, Sumpter R Jr, et al. Control of antiviral defenses through hepatitis C virus disruption of retinoic acid-inducible gene-I signaling. Proc Natl Acad Sci U S A. 2005;102:2986–2991.
   PubMed Web of Science ®Google Scholar
• Li K, Foy E, Ferreon JC, et al. Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIF. Proc Natl Acad Sci U S A. 2005;102:2992–2997.
   PubMed Web of Science ®Google Scholar
• Bode JG, Ludwig S, Ehrhardt C, et al. IFN-alpha antagonistic activity of HCV core protein involves induction of suppressor of cytokine signaling-3. Faseb J. 2003;17:488–490.
   PubMed Web of Science ®Google Scholar
• Heim MH, Moradpour D, Blum HE. Expression of hepatitis C virus proteins inhibits signal transduction through the Jak-STAT pathway. J Virol. 1999;73:8469–8475.
   PubMed Web of Science ®Google Scholar
• Taylor DR, Shi ST, Romano PR, et al. Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein. Science. 1999;285:107–110.
   PubMed Web of Science ®Google Scholar
• Gonzalez-Anon M, Cervera-Deval J, Garcia-Vila JH, et al. Characterization of solid liver lesions with color and pulsed Doppler imaging. Abdom Imaging. 1999;24:137–143.
   PubMedGoogle Scholar
• Rehermann B. Pathogenesis of chronic viral hepatitis: differential roles of T cells and NK cells. Nat Med. 2013;19:859–868.
   PubMed Web of Science ®Google Scholar
• Chang KM, Thimme R, Melpolder JJ, et al. Differential CD4(+) and CD8(+) T-cell responsiveness in hepatitis C virus infection. Hepatology. 2001;33:267–276.
   PubMed Web of Science ®Google Scholar
• Thimme R, Bukh J, Spangenberg HC, et al. Viral and immunological determinants of hepatitis C virus clearance, persistence, and disease. Proc Natl Acad Sci U S A. 2002;99:15661–15668.
   PubMed Web of Science ®Google Scholar
• Penna A, Del Prete G, Cavalli A, et al. Predominant T-helper 1 cytokine profile of hepatitis B virus nucleocapsid-specific T cells in acute self-limited hepatitis B. Hepatology. 1997;25:1022–1027.
   PubMed Web of Science ®Google Scholar
• Asabe S, Wieland SF, Chattopadhyay PK, et al. The size of the viral inoculum contributes to the outcome of hepatitis B virus infection. J Virol. 2009;83:9652–9662.
   PubMed Web of Science ®Google Scholar
• 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;77:68–76.
   PubMed Web of Science ®Google Scholar
• McMahan RH, Golden-Mason L, Nishimura MI, et al. Tim-3 expression on PD-1+ HCV-specific human CTLs is associated with viral persistence, and its blockade restores hepatocyte-directed in vitro cytotoxicity. J Clin Invest. 2010;120:4546–4557.
   PubMed Web of Science ®Google Scholar
• Folgori A, Spada E, Pezzanera M, et al. Early impairment of hepatitis C virus specific T cell proliferation during acute infection leads to failure of viral clearance. Gut. 2006;55:1012–1019.
   PubMed Web of Science ®Google Scholar
• Bowen DG, Walker CM. Mutational escape from CD8+ T cell immunity: HCV evolution, from chimpanzees to man. J Exp Med. 2005;201:1709–1714.
   PubMed Web of Science ®Google Scholar
• Sarobe P, Lasarte JJ, Casares N, et al. Abnormal priming of CD4(+) T cells by dendritic cells expressing hepatitis C virus core and E1 proteins. J Virol. 2002;76:5062–5070.
   PubMed Web of Science ®Google Scholar
• Boettler T, Spangenberg HC, Neumann-Haefelin C, et al. T cells with a CD4+CD25+ regulatory phenotype suppress in vitro proliferation of virus-specific CD8+ T cells during chronic hepatitis C virus infection. J Virol. 2005;79:7860–7867.
   PubMed Web of Science ®Google Scholar
• Shin EC, Sung PS, Park SH. Immune responses and immunopathology in acute and chronic viral hepatitis. Nat Rev Immunol. 2016;16:509–523.
   PubMed Web of Science ®Google Scholar
• You Q, Cheng L, Kedl RM, et al. Mechanism of T cell tolerance induction by murine hepatic Kupffer cells. Hepatology. 2008;48:978–990.
   PubMed Web of Science ®Google Scholar
• Yang G, Liu A, Xie Q, et al. Association of CD4+CD25+Foxp3+ regulatory T cells with chronic activity and viral clearance in patients with hepatitis B. Int Immunol. 2007;19:133–140.
   PubMed Web of Science ®Google Scholar
• Bolacchi F, Sinistro A, Ciaprini C, et al. Increased hepatitis C virus (HCV)-specific CD4+CD25+ regulatory T lymphocytes and reduced HCV-specific CD4+ T cell response in HCV-infected patients with normal versus abnormal alanine aminotransferase levels. Clin Exp Immunol. 2006;144:188–196.
   PubMed Web of Science ®Google Scholar
• Farci P, Alter HJ, Govindarajan S, et al. Lack of protective immunity against reinfection with hepatitis C virus. Science. 1992;258:135–140.
   PubMed Web of Science ®Google Scholar
• Neumann-Haefelin C, Timm J, Spangenberg HC, et al. Virological and immunological determinants of intrahepatic virus-specific CD8+ T-cell failure in chronic hepatitis C virus infection. Hepatology. 2008;47:1824–1836.
   PubMed Web of Science ®Google Scholar
• Wahid A, Dubuisson J. Virus-neutralizing antibodies to hepatitis C virus. J Viral Hepat. 2013;20:369–376.
   PubMed Web of Science ®Google Scholar
• Dunn C, Peppa D, Khanna P, et al. Temporal analysis of early immune responses in patients with acute hepatitis B virus infection. Gastroenterology. 2009;137:1289–1300.
   PubMed Web of Science ®Google Scholar
• Chisari FV, Isogawa M, Wieland SF. Pathogenesis of hepatitis B virus infection. Pathol Biol (Paris). 2010;58:258–266.
   PubMed Web of Science ®Google Scholar
• Hosel M, Quasdorff M, Wiegmann K, et al. Not interferon, but interleukin-6 controls early gene expression in hepatitis B virus infection. Hepatology. 2009;50:1773–1782.
   PubMed Web of Science ®Google Scholar
• Kumar M, Jung SY, Hodgson AJ, et al. Hepatitis B virus regulatory HBx protein binds to adaptor protein IPS-1 and inhibits the activation of beta interferon. J Virol. 2011;85:987–995.
   PubMed Web of Science ®Google Scholar
• Wu J, Meng Z, Jiang M, et al. Hepatitis B virus suppresses toll-like receptor-mediated innate immune responses in murine parenchymal and nonparenchymal liver cells. Hepatology. 2009;49:1132–1140.
   PubMed Web of Science ®Google Scholar
• Visvanathan SNA, Thompson AJ, Riordan SM, et al. Regulation of Toll-like receptor-2 expression in chronic hepatitis B by the precore protein. Hepatology. 2007;45:102–110.
   PubMed Web of Science ®Google Scholar
• Thompson AJ, Colledge D, Rodgers S, et al. Stimulation of the interleukin-1 receptor and Toll-like receptor 2 inhibits hepatitis B virus replication in hepatoma cell lines in vitro. Antivir Ther. 2009;14:797–808.
   PubMed Web of Science ®Google Scholar
• Isogawa M, Robek MD, Furuichi Y, et al. Toll-like receptor signaling inhibits hepatitis B virus replication in vivo. J Virol. 2005;79:7269–7272.
   PubMed Web of Science ®Google Scholar
• Gane EJ, Lim YS, Gordon SC, et al. The oral toll-like receptor-7 agonist GS-9620 in patients with chronic hepatitis B virus infection. J Hepatol. 2015;63:320–328.
   PubMed Web of Science ®Google Scholar
• Peppa D, Micco L, Javaid A, et al. Blockade of immunosuppressive cytokines restores NK cell antiviral function in chronic hepatitis B virus infection. Plos Pathog. 2010;6:e1001227.
   PubMed Web of Science ®Google Scholar
• Guidotti LG, Rochford R, Chung J, et al. Viral clearance without destruction of infected cells during acute HBV infection. Science. 1999;284:825–829.
   PubMed Web of Science ®Google Scholar
• Phillips S, Chokshi S, Riva A, et al. CD8(+) T cell control of hepatitis B virus replication: direct comparison between cytolytic and noncytolytic functions. J Immunol. 2010;184:287–295.
   PubMed Web of Science ®Google Scholar
• Levrero M, Pollicino T, Petersen J, et al. Control of cccDNA function in hepatitis B virus infection. J Hepatol. 2009;51:581–592.
   PubMed Web of Science ®Google Scholar
• Schuttler CG, Fiedler N, Schmidt K, et al. Suppression of hepatitis B virus enhancer 1 and 2 by hepatitis C virus core protein. J Hepatol. 2002;37:855–862.
   PubMed Web of Science ®Google Scholar
• Alberti A, Diana S, Sculard GH, et al. Detection of a new antibody system reacting with Dane particles in hepatitis B virus infection. Br Med J. 1978;2:1056–1058.
   PubMed Web of Science ®Google Scholar
• Grady GF, Lee VA, Prince AM, et al. Hepatitis B immune globulin for accidental exposures among medical personnel: final report of a multicenter controlled trial. J Infect Dis. 1978;138:625–638.
   PubMed Web of Science ®Google Scholar
• Glebe D, Lorenz H, Gerlich WH, et al. Correlation of virus and host response markers with circulating immune complexes during acute and chronic woodchuck hepatitis virus infection. J Virol. 2009;83:1579–1591.
   PubMed Web of Science ®Google Scholar
• Mason W, Litwin S. Pathogenesis of Hepadnavirus Infections. In: Lai C, Locarnini S, editors. Hepatitis B Virus. London (UK): International Medical Press; 2002. p. 99–114.
   Google Scholar
• Xu X, Shang Q, Chen X, et al. Reversal of B-cell hyperactivation and functional impairment is associated with HBsAg seroconversion in chronic hepatitis B patients. Cell Mol Immunol. 2015;12:309–316.
   PubMed Web of Science ®Google Scholar
• Shih CM, Lo SJ, Miyamura T, et al. Suppression of hepatitis B virus expression and replication by hepatitis C virus core protein in HuH-7 cells. J Virol. 1993;67:5823–5832.
   PubMed Web of Science ®Google Scholar
• Shih CM, Chen CM, Chen SY, et al. Modulation of the trans-suppression activity of hepatitis C virus core protein by phosphorylation. J Virol. 1995;69:1160–1171.
   PubMed Web of Science ®Google Scholar
• Chen SY, Kao CF, Chen CM, et al. Mechanisms for inhibition of hepatitis B virus gene expression and replication by hepatitis C virus core protein. J Biol Chem. 2003;278:591–607.
   PubMed Web of Science ®Google Scholar
• Pan Y, Wei W, Kang L, et al. NS5A protein of HCV enhances HBV replication and resistance to interferon response. Biochem Biophys Res Commun. 2007;359:70–75.
   PubMed Web of Science ®Google Scholar
• Guo H, Zhou T, Jiang D, et al. Regulation of hepatitis B virus replication by the phosphatidylinositol 3-kinase-akt signal transduction pathway. J Virol. 2007;81:10072–10080.
   PubMed Web of Science ®Google Scholar
• Kandathil AJ, Graw F, Quinn J, et al. Use of laser capture microdissection to map hepatitis C virus-positive hepatocytes in human liver. Gastroenterology. 2013;145:1404-1413, e1401-1410.
   PubMed Web of Science ®Google Scholar
• Agnello V, Abel G, Knight GB, et al. Detection of widespread hepatocyte infection in chronic hepatitis C. Hepatology. 1998;28:573–584.
   PubMed Web of Science ®Google Scholar
• Rodriguez-Inigo E, Mariscal L, Bartolome J, et al. Distribution of hepatitis B virus in the liver of chronic hepatitis C patients with occult hepatitis B virus infection. J Med Virol. 2003;70:571–580.
   PubMed Web of Science ®Google Scholar
• Cheng PN, Liu WC, Tsai HW, et al. Association of intrahepatic cccDNA reduction with the improvement of liver histology in chronic hepatitis B patients receiving oral antiviral agents. J Med Virol. 2011;83:602–607.
   PubMed Web of Science ®Google Scholar
• Eyre NS, Phillips RJ, Bowden S, et al. Hepatitis B virus and hepatitis C virus interaction in Huh-7 cells. J Hepatol. 2009;51:446–457.
   PubMed Web of Science ®Google Scholar
• Bellecave P, Gouttenoire J, Gajer M, et al. Hepatitis B and C virus coinfection: a novel model system reveals the absence of direct viral interference. Hepatology. 2009;50:46–55.
   PubMed Web of Science ®Google Scholar
• Rodriguez-Inigo E, Bartolome J, Ortiz-Movilla N, et al. Hepatitis C virus (HCV) and hepatitis B virus (HBV) can coinfect the same hepatocyte in the liver of patients with chronic HCV and occult HBV infection. J Virol. 2005;79:15578–15581.
   PubMed Web of Science ®Google Scholar
• Wieland SF, Asabe S, Engle RE, et al. Limited hepatitis B virus replication space in the chronically hepatitis C virus-infected liver. J Virol. 2014;88:5184–5188.
   PubMed Web of Science ®Google Scholar
• Brotman B, Prince AM, Huima T, et al. Interference between non-A, non-B and hepatitis B virus infection in chimpanzees. J Med Virol. 1983;11:191–205.
   PubMed Web of Science ®Google Scholar
• Bradley DW, Maynard JE, McCaustland KA, et al. Non-A, non-B hepatitis in chimpanzees: interference with acute hepatitis A virus and chronic hepatitis B virus infections. J Med Virol. 1983;11:207–213.
   PubMed Web of Science ®Google Scholar
• Liaw YF, Lin SM, Sheen IS, et al. Acute hepatitis C virus superinfection followed by spontaneous HBeAg seroconversion and HBsAg elimination. Infection. 1991;19:250–251.
   PubMed Web of Science ®Google Scholar
• Fattovich G, Tagger A, Brollo L, et al. Hepatitis C virus infection in chronic hepatitis B virus carriers. J Infect Dis. 1991;163:400–402.
   PubMed Web of Science ®Google Scholar
• Sato S, Fujiyama S, Tanaka M, et al. Coinfection of hepatitis C virus in patients with chronic hepatitis B infection. J Hepatol. 1994;21:159–166.
   PubMed Web of Science ®Google Scholar
• Sheen IS, Liaw YF, Chu CM, et al. Role of hepatitis C virus infection in spontaneous hepatitis B surface antigen clearance during chronic hepatitis B virus infection. J Infect Dis. 1992;165:831–834.
   PubMed Web of Science ®Google Scholar
• Chu CM, Yeh CT, Liaw YF. Low-level viremia and intracellular expression of hepatitis B surface antigen (HBsAg) in HBsAg carriers with concurrent hepatitis C virus infection. J Clin Microbiol. 1998;36:2084–2086.
   PubMed Web of Science ®Google Scholar
• Jardi R, Rodriguez F, Buti M, et al. Role of hepatitis B, C, and D viruses in dual and triple infection: influence of viral genotypes and hepatitis B precore and basal core promoter mutations on viral replicative interference. Hepatology. 2001;34:404–410.
   PubMed Web of Science ®Google Scholar
• Chen F, Zhang J, Wen B, et al. HBV/HCV dual infection impacts viral load, antibody response, and cytokine expression differently from HBV or HCV single infection. Sci Rep. 2016;6:39409.
   PubMed Web of Science ®Google Scholar
• Ohkawa K, Hayashi N, Yuki N, et al. Hepatitis C virus antibody and hepatitis C virus replication in chronic hepatitis B patients. J Hepatol. 1994;21:509–514.
   PubMed Web of Science ®Google Scholar
• Ohkawa K, Hayashi N, Yuki N, et al. Long-term follow-up of hepatitis B virus and hepatitis C virus replicative levels in chronic hepatitis patients coinfected with both viruses. J Med Virol. 1995;46:258–264.
   PubMed Web of Science ®Google Scholar
• Crespo J, Lozano JL, De La Cruz F, et al. Prevalence and significance of hepatitis C viremia in chronic active hepatitis B. Am J Gastroenterol. 1994;89:1147–1151.
   PubMed Web of Science ®Google Scholar
• Zarski JP, Bohn B, Bastie A, et al. Characteristics of patients with dual infection by hepatitis B and C viruses. J Hepatol. 1998;28:27–33.
   PubMed Web of Science ®Google Scholar
• Yu G, Chi X, Wu R, et al. Replication inhibition of Hepatitis B virus and Hepatitis C virus in co-infected patients in Chinese population. Plos One. 2015;10:e0139015.
   PubMed Web of Science ®Google Scholar
• Pontisso P, Gerotto M, Ruvoletto MG, et al. Hepatitis C genotypes in patients with dual hepatitis B and C virus infection. J Med Virol. 1996;48:157–160.
   PubMed Web of Science ®Google Scholar
• Raimondo G, Brunetto MR, Pontisso P, et al. Longitudinal evaluation reveals a complex spectrum of virological profiles in hepatitis B virus/hepatitis C virus-coinfected patients. Hepatology. 2006;43:100–107.
   PubMed Web of Science ®Google Scholar
• 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. 1998;75:347–354.
   PubMed Web of Science ®Google Scholar
• Agrawal A, Samrat SK, Agrawal B, et al. Co-incubation with core proteins of HBV and HCV leads to modulation of human dendritic cells. Viral Immunol. 2014;27:412–417.
   PubMed Web of Science ®Google Scholar
• Chu CM, Sheen IS, Liaw YF. Low-level hepatitis C viremia and humoral immune response to NS4 in chronic hepatitis B virus-hepatitis C virus coinfection. Scand J Gastroenterol. 2004;39:778–782.
   PubMed Web of Science ®Google Scholar
• McMahon BJ. Epidemiology and natural history of hepatitis B. Semin Liver Dis. 2005;25(Suppl 1):3–8.
   PubMed Web of Science ®Google Scholar
• Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2095–2128.
   PubMed Web of Science ®Google Scholar
• Delmas J, Schorr O, Jamard C, et al. Inhibitory effect of adefovir on viral DNA synthesis and covalently closed circular DNA formation in duck hepatitis B virus-infected hepatocytes in vivo and in vitro. Antimicrob Agents Chemother. 2002;46:425–433.
   PubMed Web of Science ®Google Scholar
• Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958–965.
   PubMed Web of Science ®Google Scholar
• Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975–982.
   PubMed Web of Science ®Google Scholar
• McHutchison JG, Gordon SC, Schiff ER, et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med. 1998;339:1485–1492.
   PubMed Web of Science ®Google Scholar
• Holmes JA, Desmond PV, Thompson AJ. Interferon-free combination therapies for the treatment of hepatitis C: current insights. Hepatic Med Evid Res. 2015. Accepted for publication 23rd March 2015, DOI pending.
   PubMedGoogle Scholar
• Rijckborst V, Janssen HLA. The role of interferon in Hepatitis B therapy. Curr Hepat Rep. 2010;9:231–238.
   PubMedGoogle Scholar
• Rehermann B, Bertoletti A. Immunological aspects of antiviral therapy of chronic hepatitis B virus and hepatitis C virus infections. Hepatology. 2015;61:712–721.
   PubMed Web of Science ®Google Scholar
• Meissner EG, Wu D, Osinusi A, et al. Endogenous intrahepatic IFNs and association with IFN-free HCV treatment outcome. J Clin Invest. 2014;124:3352–3363.
   PubMed Web of Science ®Google Scholar
• Meissner EG, Kohli A, Virtaneva K, et al. Achieving sustained virologic response after interferon-free hepatitis C virus treatment correlates with hepatic interferon gene expression changes independent of cirrhosis. J Viral Hepat. 2016;23:496–505.
   PubMed Web of Science ®Google Scholar
• Serti E, Chepa-Lotrea X, Kim YJ, et al. Successful interferon-free therapy of chronic Hepatitis C virus infection normalizes natural killer cell function. Gastroenterology. 2015;149:190–200, e192.
   PubMed Web of Science ®Google Scholar
• Spaan M, Van Oord G, Kreefft K, et al. Immunological analysis during interferon-free therapy for chronic Hepatitis C virus infection reveals modulation of the natural killer cell compartment. J Infect Dis. 2016;213:216–223.
   PubMed Web of Science ®Google Scholar
• Burchill MA, Golden-Mason L, Wind-Rotolo M, et al. Memory re-differentiation and reduced lymphocyte activation in chronic HCV-infected patients receiving direct-acting antivirals. J Viral Hepat. 2015;22:983–991.
   PubMed Web of Science ®Google Scholar
• Martin B, Hennecke N, Lohmann V, et al. Restoration of HCV-specific CD8+ T cell function by interferon-free therapy. J Hepatol. 2014;61:538–543.
   PubMed Web of Science ®Google Scholar
• Ou P, Fang Z, Chen J. Hepatitis B reactivation in a chronic hepatitis C patient treated with ledipasvir and sofosbuvir: a case report. Clin Res Hepatol Gastroenterol. 2017;41(2):e17–e18.
   PubMed Web of Science ®Google Scholar
• Liu JY, Sheng YJ, Hu HD, et al. The influence of hepatitis B virus on antiviral treatment with interferon and ribavirin in Asian patients with hepatitis C virus/hepatitis B virus coinfection: a meta-analysis. Virol J. 2012;9:186.
   PubMed Web of Science ®Google Scholar
• Chen G, Wang C, Chen J, et al. Hepatitis B reactivation in hepatitis B and C coinfected patients treated with antiviral agents: A systematic review and meta-analysis. Hepatology. 2017. Doi:10.1002/hep.29109.
   Google Scholar
• Lok AS, Liang RH, Chiu EK, et al. Reactivation of hepatitis B virus replication in patients receiving cytotoxic therapy. Report of a prospective study. Gastroenterology. 1991;100:182–188.
   PubMed Web of Science ®Google Scholar
• Yeo W, Chan PK, Zhong S, et al. 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.
   PubMed Web of Science ®Google Scholar
• Perrillo RP. Acute flares in chronic hepatitis B: the natural and unnatural history of an immunologically mediated liver disease. Gastroenterology. 2001;120:1009–1022.
   PubMed Web of Science ®Google Scholar
• Vento S, Cainelli F, Longhi MS. Reactivation of replication of hepatitis B and C viruses after immunosuppressive therapy: an unresolved issue. Lancet Oncol. 2002;3:333–340.
   PubMed Web of Science ®Google Scholar
• Hoofnagle JH. Reactivation of hepatitis B. Hepatology. 2009;49:S156–165.
   PubMed Web of Science ®Google Scholar
• Loomba R, Rowley A, Wesley R, et al. Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy. Ann Intern Med. 2008;148:519–528.
   PubMed Web of Science ®Google Scholar
• Reddy KR, Beavers KL, Hammond SP, et al. American Gastroenterological Association Institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2015;148:215-219; quiz e216-217.
   Web of Science ®Google Scholar
• Paul S, Saxena A, Terrin N, et al. Hepatitis B virus reactivation and prophylaxis during solid tumor chemotherapy: a systematic review and meta-analysis. Ann Intern Med. 2016;164:30–40.
   PubMed Web of Science ®Google Scholar
• Huang YH, Hsiao LT, Hong YC, et al. Randomized controlled trial of entecavir prophylaxis for rituximab-associated hepatitis B virus reactivation in patients with lymphoma and resolved hepatitis B. J Clin Oncol. 2013;31:2765–2772.
   PubMed Web of Science ®Google Scholar
• Cheng AL, Hsiung CA, Su IJ, et al. Steroid-free chemotherapy decreases risk of hepatitis B virus (HBV) reactivation in HBV-carriers with lymphoma. Hepatology. 2003;37:1320–1328.
   PubMed Web of Science ®Google Scholar
• Jang JW, Choi JY, Bae SH, et al. A randomized controlled study of preemptive lamivudine in patients receiving transarterial chemo-lipiodolization. Hepatology. 2006;43:233–240.
   PubMed Web of Science ®Google Scholar
• Perez-Alvarez R, Diaz-Lagares C, Garcia-Hernandez F, et al. Hepatitis B virus (HBV) reactivation in patients receiving tumor necrosis factor (TNF)-targeted therapy: analysis of 257 cases. Medicine (Baltimore). 2011;90:359–371.
   PubMed Web of Science ®Google Scholar
• Koutsianas C, Thomas K, Vassilopoulos D. Hepatitis B reactivation in rheumatic diseases: screening and prevention. Rheum Dis Clin North Am. 2017;43:133–149.
   PubMed Web of Science ®Google Scholar
• Bessone F, Dirchwolf M. Management of hepatitis B reactivation in immunosuppressed patients: an update on current recommendations. World J Hepatol. 2016;8:385–394.
   PubMed Web of Science ®Google Scholar
• Trowsdale J, Betz AG. Mother’s little helpers: mechanisms of maternal-fetal tolerance. Nat Immunol. 2006;7:241–246.
   PubMed Web of Science ®Google Scholar
• Giles M, Visvanathan K, Lewin S, et al. Clinical and virological predictors of hepatic flares in pregnant women with chronic hepatitis B. Gut. 2015;64:1810–1815.
   PubMed Web of Science ®Google Scholar