Relation of Reduction of Antibodies against Hepatitis B Virus to Hepatocellular Carcinoma Recurrence in the Patients with Resolved Hepatitis B Virus Infection Following Direct-acting Antiviral Therapy for Hepatitis C Virus Infection
Citation Information :
Joko K, Mashiba T, Ochi H, Yano R, Sato K, Okujima Y, Aono M, Azemoto N, Takechi S, Yokota T, Jinoka R, Moriyama Y, Nishiyama M. Relation of Reduction of Antibodies against Hepatitis B Virus to Hepatocellular Carcinoma Recurrence in the Patients with Resolved Hepatitis B Virus Infection Following Direct-acting Antiviral Therapy for Hepatitis C Virus Infection. Euroasian J Hepatogastroenterol 2019; 9 (2):78-83.
Background: A possible interaction of hepatitis viruses at cellular and molecular levels has been suggested. Eradication of hepatitis C virus (HCV) has been reported to induce activation of hepatitis B virus (HBV)-related liver diseases. Materials and methods: The present study examined association of HBV markers with recurrence of hepatocellular carcinoma (HCC) in patients with resolved HCV infection by direct-acting antiviral (DAA) therapy. In a patient pool of 378 patients with sustained virologic response (SVR) by DAA, the antibody to the hepatitis B surface antigen (anti-HBs), the antibody to the hepatitis B core antigen (anti-HBc), and HBV-DNA levels were estimated before and at the end of DAA therapy. These patients were HBsAg negative. Eighty-nine patients had a history of curative treatment of HCC by resection or radiofrequency ablation. A Cox proportional hazards model was used to identify risk factors for HCC recurrence, including the change ratio of the antibody against HBV proteins. Results: Although 188 patients had resolved HBV infection, no patient showed HBV reactivation, but anti-HBs and anti-HBc levels decreased significantly. No significant difference in the HCC recurrence rate was evident between patients with and without resolved HBV infection. Changes of immune responses to HBV proteins did not affect HCC recurrence after DAA therapy for HCV infection in this cohort. Conclusion: The mechanisms underlying diverse roles of DAA-induced SVR of HCV on HBV kinetics need to be resolved in future.
Kasahara A, Higashi N, Mochizuki K, et al. Risk factors for hepatocellular carcinoma and its incidence after interferon treatment in patients with chronic hepatitis C. Osaka Liver Disease Study Group. Hepatology 1998;27(5):1394–1402. DOI: 10.1002/hep.510270529.
Ikeda K, Saitoh S, Arase Y, et al. Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C: a long-term observation study of 1,643 patients using statistical bias correction with proportional hazard analysis. Hepatology 1999;29(4):1124–1130. DOI: 10.1002/hep.510290439.
Yoshida H, Shiratori Y, Moriyama M, et al. Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. IHIT Study Group. Inhibition of hepatocarcinogenesis by interferon therapy. Ann Intern Med 1999;131(3):174–181. DOI: 10.7326/0003-4819-131-3-199908030-00003.
Morgan RL, Baack B, Smith BD, et al. Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: a meta-analysis of observational studies. Ann Intern Med 2013; 158(5 Pt 1):329–337. DOI: 10.7326/0003-4819-158-5-201303050-00005.
Tong MJ, Theodoro CF, Salvo RT. Late development of hepatocellular carcinoma after viral clearance in patients with chronic hepatitis C: a need for continual surveillance. J Dig Dis 2018;19(7):411–420. DOI: 10.1111/1751-2980.12615.
Kudo M. Impact of interferon therapy after curative treatment of hepatocellular carcinoma. Oncology 2008;75(Suppl 1):30–41. DOI: 10.1159/000173422.
Breitenstein S, Dimitroulis D, Petrowsky H, et al. Systematic review and meta-analysis of interferon after curative treatment of hepatocellular carcinoma in patients with viral hepatitis. Br J Surg 2009;96(9): 975–981. DOI: 10.1002/bjs.6731.
Shen YC, Hsu C, Chen LT, et al. Adjuvant interferon therapy after curative therapy for hepatocellular carcinoma (HCC): a meta-regression approach. J Hepatol 2010;52(6):889–894. DOI: 10.1016/j.jhep.2009.12.041.
Miyake Y, Takaki A, Iwasaki Y, et al. Meta-analysis: interferon-alpha prevents the recurrence after curative treatment of hepatitis C virus-related hepatocellular carcinoma. J Viral Hepat 2010;17(4):287–292. DOI: 10.1111/j.1365-2893.2009.01181.x.
Joko K, Goto T, Watanabe H, et al. Effects of antiviral therapy for hepatitis C following treatment of hepatocellular carcinoma: survey findings of the Japanese Red Cross Liver Study Group. Hepatol Res 2016;46(4):251–258. DOI: 10.1111/hepr.12515.
Kanwal F, Kramer J, Asch SM, et al. Risk of hepatocellular cancer in HCV patients treated with direct-acting antiviral agents. Gastroenterology 2017;153(4):996–1005. DOI: 10.1053/j.gastro.2017.06.012.
Kozbial K, Moser S, Schwarzer R, et al. Unexpected high incidence of hepatocellular carcinoma in cirrhotic patients with sustained virologic response following interferon-free direct-acting antiviral treatment. J Hepatol 2016;65(4):856–858. DOI: 10.1016/j.jhep.2016.06.009.
Conti F, Buonfiglioli F, Scuteri A, et al. Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals. J Hepatol 2016;65(4):727–733. DOI: 10.1016/j.jhep.2016.06.015.
Reig M, Mariño Z, Perelló C, et al. Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy. J Hepatol 2016;65(4):719–726. DOI: 10.1016/j.jhep.2016.04.008.
Yang J, Aqel BA, Pungpapong S, et al. Direct acting antiviral therapy and tumor recurrence after liver transplantation for hepatitis C-associated hepatocellular carcinoma. J Hepatol 2016;65(4):859–860. DOI: 10.1016/j.jhep.2016.06.023.
El Kassas M, Funk AL, Salaheldin M, et al. Increased recurrence rates of hepatocellular carcinoma after DAA therapy in a hepatitis C-infected Egyptian cohort: a comparative analysis. J Viral Hepat 2018;25(6):623–630. DOI: 10.1111/jvh.12854.
Ravi S, Axley P, Jones D, et al. Unusually high rates of hepatocellular carcinoma after treatment with direct-acting antiviral therapy for hepatitis C related cirrhosis. Gastroenterology 2017;152(4):911–912. DOI: 10.1053/j.gastro.2016.12.021.
Abdelaziz AO, Nabil MM, Abdelmaksoud AH, et al. Tumor behavior of hepatocellular carcinoma after hepatitis C treatment by direct-acting antivirals: comparative analysis with non-direct-acting antivirals-treated patients. Eur J Gastroenterol Hepatol 2019;31(1):75–79. DOI: 10.1097/MEG.0000000000001264.
ANRS collaborative study group on hepatocellular carcinoma (ANRS CO22 HEPATHER, CO12 CirVir and CO23 CUPILT cohorts). Lack of evidence of an effect of direct-acting antivirals on the recurrence of hepatocellular carcinoma: Data from three ANRS cohorts. J Hepatol 2016;65(4):734–740. DOI: 10.1016/j.jhep.2016.05.045.
Li DK, Ren Y, Fierer DS, et al. The short-term incidence of hepatocellular carcinoma is not increased after hepatitis C treatment with direct-acting antivirals: an ERCHIVES study. Hepatology 2017;67(6):2244–2253. DOI: 10.1002/hep.29707.
Mashiba T, Joko K, Kurosaki M, et al. Does interferon-free direct-acting antiviral therapy for hepatitis C after curative treatment for hepatocellular carcinoma lead to unexpected recurrences of HCC? A multicenter study by the Japanese Red Cross Hospital Liver Study Group. PLoS One 2018;13(4):e0194704. DOI: 10.1371/journal.pone.0194704.
Nishibatake Kinoshita M, Minami T, Tateishi R, et al. Impact of direct-acting antivirals on early recurrence of HCV-related HCC: Comparison with interferon-based therapy. J Hepatol 2018;70(1):78–86. DOI: 10.1016/j.jhep.2018.09.029.
Hollande C, Pol S. Editorial: reciprocal interaction between HCV direct-acting anti-virals (DAA) and hepatocellular carcinoma (HCC)-a negative impact of HCC on sustained virologic response not of DAA on HCC. Aliment Pharmacol Ther 2019;50(2):227–228. DOI: 10.1111/apt.15328.
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(8):1304–1306. DOI: 10.1093/cid/civ474.
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(5):489–491. DOI: 10.1111/hepr.12578.
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. DOI: 10.1186/s13256-015-0630-8.
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. DOI: 10.1016/j.jcv.2016.02.026.
Tamori A, Abiru S, Enomoto H, et al. Low incidence of hepatitis B virus reactivation and subsequent hepatitis in patients with chronic hepatitis C receiving direct-acting antiviral therapy. J Viral Hepat 2018;25(5):608–611. DOI: 10.1111/jvh.12840.
Holmes JA, Carlton-Smith C, Kim AY, et al. Dynamic changes in innate immune responses during direct-acting antiviral therapy for HCV infection. J Viral Hepat 2019;26(3):362–372. DOI: 10.1111/jvh.13041.
Belperio PS, Shahoumian TA, Mole LA, et al. Evaluation of hepatitis B reactivation among 62,920 veterans treated with oral hepatitis C antivirals. Hepatology 2017;66(1):27–36. DOI: 10.1002/hep.29135.
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;66(1):13–26. DOI: 10.1002/hep.29109.
Mücke MM, Backus LI, Mücke VT, et al. Hepatitis B virus reactivation during direct-acting antiviral therapy for hepatitis C: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2018;3(3):172–180. DOI: 10.1016/S2468-1253(18)30002-5.
Kawagishi N, Suda G, Onozawa M, et al. Comparing the risk of hepatitis B virus reactivation between direct-acting antiviral therapies and interferon-based therapies for hepatitis C. J Viral Hepat 2017;24(12):1098–1106. DOI: 10.1111/jvh.12737.
Ogawa E, Furusyo N, Murata M, et al. Potential risk of HBV reactivation in patients with resolved HBV infection undergoing direct-acting antiviral treatment for HCV. Liver Int 2018;38(1):76–83. DOI: 10.1111/liv.13496.
Doi A, Sakamori R, Tahata Y, et al. Frequency of, and factors associated with, hepatitis B virus reactivation in hepatitis C patients treated with all-oral direct-acting antivirals: analysis of a Japanese prospective cohort. Hepatol Res 2017;47(13):1438–1444. DOI: 10.1111/hepr. 12919.
Bruix J, Sherman M, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology 2011;53(3):1020–1022. DOI: 10.1002/hep.24199.
Mücke MM, Mücke VT, Lange CM, et al. Managing hepatitis C in patients with the complications of cirrhosis. Liver Int 2018;38(Suppl 1):14–20. DOI: 10.1111/liv.13636.
Roche B, Coilly A, Duclos-Vallee JC, et al. The impact of treatment of hepatitis C with DAAs on the occurrence of HCC. Liver Int 2018;38(Suppl 1):139–145. DOI: 10.1111/liv.13659.
Huang AC, Mehta N, Dodge JL, et al. Direct-acting antivirals do not increase the risk of hepatocellular carcinoma recurrence after local-regional therapy or liver transplant waitlist dropout. Hepatology 2018;68(2):449–461. DOI: 10.1002/hep.29855.
Toyoda H, Kumada T, Tada T, et al. The impact of HCV eradication by direct-acting antivirals on the transition of precancerous hepatic nodules to HCC: A prospective observational study. Liver Int 2018;39(3):448–454. DOI: 10.1111/liv.13987.
Ooka Y, Miho K, Shuntaro O, et al. Prediction of the very early occurrence of HCC right after DAA therapy for HCV infection. Hepatol Int 2018;12(6):523–530. DOI: 10.1007/s12072-018-9895-5.
Nahon P, Layese R, Bourcier V, et al. Incidence of hepatocellular carcinoma after direct antiviral therapy for HCV in patients with cirrhosis included in surveillance programs. Gastroenterology 2018;155(5):1436.e1–1450.e6. DOI: 10.1053/j.gastro.2018.07.015.
Calvaruso V, Cabibbo G, Cacciola I, et al. Incidence of hepatocellular carcinoma in patients with HCV-associated cirrhosis treated with direct-acting antiviral agents. Gastroenterology 2018;155: 411e.1–421.e4. DOI: 10.1053/j.gastro.2018.04.008.
Spaan M, Oord GV, Kreefft K, et al. Immunological analysis during interferon-free therapy for chronic hepatitis C virus infection reveals modulation of the natural killer cell component. J Infect Dis 2016;213(2):216–223. DOI: 10.1093/infdis/jiv391.
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(1):190–200. DOI: 10.1053/j.gastro.2015.03.004.
Emamaullee JA, Bral M, Meeberg G, et al. HCV eradication with direct-acting antivirals does not impact HCC progression on the waiting list or HCC recurrence after liver transplantation. Can J Gastroenterol Hepatol 2019;2019:2509059. DOI: 10.1155/2019/2509059.
Joko K, Mashiba T, Ochi H, et al. Influence of reduced immune response to hepatitis B virus on hepatocellular carcinoma recurrence during direct acting antiviral treatment for hepatitis C virus infection. Hepatology 2018;68(S1):1513.