REFERENCES
1. Burra P, Giannini EG, Caraceni P, Ginanni Corradini S, Rendina M, et al. Specific issues concerning the management of patients on the waiting list and after liver transplantation. Liver Int 2018;38:1338-62.
2. Foster GR, Irving WL, Cheung MC, Walker AJ, Hudson BE, et al. Impact of direct acting antiviral therapy in patients with chronic hepatitis C and decompensated cirrhosis. J Hepatol 2016;64:1224-31.
3. Manns M, Samuel D, Gane EJ, Mutimer D, McCaughan G, et al. Ledipasvir and sofosbuvir plus ribavirin in patients with genotype 1 or 4 hepatitis C virus infection and advanced liver disease: a multicentre, open-label, randomised, phase 2 trial. Lancet Infect Dis 2016;16:685-97.
4. Pawlotsky JM. New hepatitis C therapies: the toolbox, strategies, and challenges. Gastroenterology 2014;146:1176-92.
5. Poordad F, Schiff ER, Vierling JM, Landis C, Fontana RJ, et al. Daclatasvir with sofosbuvir and ribavirin for hepatitis C virus infection with advanced cirrhosis or post-liver transplantation recurrence. Hepatology 2016;63:1493-505.
6. Afdhal N, Everson GT, Calleja JL, McCaughan GW, Bosch J, et al. Effect of viral suppression on hepatic venous pressure gradient in hepatitis C with cirrhosis and portal hypertension. J Viral Hepat 2017;24:823-31.
7. Lens S, Alvarado-Tapias E, Mariño Z, Londoño MC, LLop E, et al. Effects of all-oral anti-viral therapy on HVPG and systemic hemodynamics in patients with hepatitis C virus-associated cirrhosis. Gastroenterology 2017;153:1273-83.
8. Mandorfer M, Kozbial K, Schwabl P, Freissmuth C, Schwarzer R, et al. Sustained virologic response to interferon-free therapies ameliorates HCV-induced portal hypertension. J Hepatol 2016;65:692-9.
9. Belli LS, Berenguer M, Cortesi PA, Strazzabosco M, Rockenschaub SR, et al. Delisting of liver transplant candidates with chronic hepatitis C after viral eradication: a European study. J Hepatol 2016;65:524-31.
10. Pascasio JM, Vinaixa C, Ferrer MT, Colmenero J, Rubin A, et al. Clinical outcomes of patients undergoing antiviral therapy while awaiting liver transplantation. J Hepatol 2017;67:1168-76.
11. Di Marco V, Calvaruso V, Ferraro D, Bavetta MG, Cabibbo G, et al. Effects of eradicating hepatitis C virus infection in patients with cirrhosis differ with stage of portal hypertension. Gastroenterology 2016;151:130-9.
12. Morgan RL, Baack B, Smith BD, Yartel A, Pitasi M, et al. Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: a meta-analysis of observational studies. Ann Intern Med 2013;158:329-37.
13. Janjua NZ, Chong M, Kuo M, Woods R, Wong J, et al. Long-term effect of sustained virological response on hepatocellular carcinoma in patients with hepatitis C in Canada. J Hepatol 2017;66:504-13.
14. Chhatwal J, Wang X, Ayer T, Kabiri M, Chung RT, et al. Hepatitis C disease burden in the United States in the era of oral direct-acting antivirals. Hepatology 2016;64:1442-50.
15. Flemming JA, Kim WR, Brosgart CL, Terrault NA. Reduction in liver transplant wait-listing in the era of direct-acting antiviral therapy. Hepatology 2017;65:804-12.
16. Younossi ZM, Park H, Dieterich D, Saab S, Ahmed A, et al. Assessment of cost of innovation versus the value of health gains associated with treatment of chronic hepatitis C in the United States: the quality-adjusted cost of care. Medicine (Baltimore) 2016;95:e5048.
17. Tapper EB, Afdhal NH, Curry MP. Before or after transplantation? A review of the cost effectiveness of treating waitlisted patients with hepatitis C. Transplantation 2017;101:933-7.
18. European Association for the Study of the Liver. EASL clinical practice guidelines: liver transplantation. J Hepatol 2016;64:433-85.
19. European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2016. J Hepatol 2017;66:153-94.
20. AASLD/IDSA HCV Guidance Panel. Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology 2015;62:932-54.
21. Cucchetti A, D’Amico G, Trevisani F, Morelli MC, Vitale A, et al. Effect of direct-acting antivirals on future occurrence of hepatocellular carcinoma in compensated cirrhotic patients. Dig Liver Dis 2018;50:156-62.
22. Afdhal N, Reddy KR, Nelson DR, Lawitz E, Gordon SC, et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med 2014;370:1483-93.
23. Charlton M, Everson GT, Flamm SL, Kumar P, Landis C, et al. Ledipasvir and sofosbuvir plus ribavirin for treatment of HCV infection in patients with advanced liver disease. Gastroenterology 2015;149:649-59.
24. Curry MP, O’Leary JG, Bzowej N, Muir AJ, Korenblat KM, et al. Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. N Engl J Med 2015;373:2618-28.
25. Feld JJ, Jacobson IM, Hézode C, Asselah T, Ruane PJ, et al. Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med 2015;373:2599-607.
26. Feld JJ, Kowdley KV, Coakley E, Sigal S, Nelson DR, et al. Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med 2014;370:1594-603.
27. Foster GR, Afdhal N, Roberts SK, Bräu N, Gane EJ, et al. Sofosbuvir and velpatasvir for HCV genotype 2 and 3 infection. N Engl J Med 2015;373:2608-17.
28. Ferenci P, Bernstein D, Lalezari J, Cohen D, Luo Y, et al. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med 2014;370:1983-92.
29. Jacobson IM, Gordon SC, Kowdley KV, Yoshida EM, Rodriguez-Torres M, et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med 2013;368:1867-77.
30. Kwo PY, Mantry PS, Coakley E, Te HS, Vargas HE, et al. An interferon-free antiviral regimen for HCV after liver transplantation. N Engl J Med 2014;371:2375-82.
31. Lawitz E, Mangia A, Wyles D, Rodriguez-Torres M, Hassanein T, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med 2013;368:1878-87.
32. Poordad F, Hezode C, Trinh R, Kowdley KV, Zeuzem S, et al. ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis. N Engl J Med 2014;370:1973-82.
33. Poordad F, Lawitz E, Kowdley KV, Cohen DE, Podsadecki T, et al. Exploratory study of oral combination antiviral therapy for hepatitis C. N Engl J Med 2013;368:45-53.
34. Sulkowski MS, Gardiner DF, Rodriguez-Torres M, Reddy KR, Hassanein T, et al. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med 2014;370:211-21.
35. Reig M, Mariño Z, Perelló C, Iñarrairaegui M, Ribeiro A, et al. Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy. J Hepatol 2016;65:719-26.
36. Ripoll C, Groszmann RJ, Garcia-Tsao G, Bosch J, Grace N, et al. Hepatic venous pressure gradient predicts development of hepatocellular carcinoma independently of severity of cirrhosis. J Hepatol 2009;50:923-8.
37. Conti F, Buonfiglioli F, Scuteri A, Crespi C, Bolondi L, et al. Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals. J Hepatol 2016;65:727-33.
38. Ioannou GN, Splan MF, Weiss NS, McDonald GB, Beretta L, et al. Incidence and predictors of hepatocellular carcinoma in patients with cirrhosis. Clin Gastroenterol Hepatol 2007;5:938-45.
39. Buonfiglioli F, Conte F, Andreone P, Crespi C, Foschi FG, et al. Development of hepatocellular carcinoma in HCV cirrhotic patients treated with direct acting antivirals. J Hepatol 2016;64:S125.
40. Cheung MCM, Walker AJ, Hudson BE, Verma S, McLauchlan J, et al. Outcomes after successful direct-acting antiviral therapy for patients with chronic hepatitis C and decompensated cirrhosis. J Hepatol 2016;65:741-7.
41. Muir AJ, Buti M, Nahass R, Agarwal K, Gane EJ, et al. Long-term follow-up of patients with chronic HCV infection and compensated or decompensated cirrhosis following treatment with sofosbuvir-based regimens. Hepatology (Baltimore, Md.) 2016;64:437A-8A.
42. Romano A, Angeli P, Piovesan S, Noventa F, Anastassopoulos G, Chemello L, et al. Newly diagnosed hepatocellular carcinoma in patients with advanced hepatitis C treated with DAAs: A prospective population study. J Hepatol 2018;69:345-52.
43. Nagaoki Y, Imamura M, Aikata H, Daijo K, Teraoka Y, et al. The risks of hepatocellular carcinoma development after HCV eradication are similar between patients treated with peg-interferon plus ribavirin and direct-acting antiviral therapy. PLoS One 2017;12:e0182710.
44. Ji D, Wang C, Shao Q, Li F, Wu V, et al. No increase in the occurrence rate of hepatocellular carcinoma in Chinese treated by direct-acting antivirals compared to interferon after eradication of hepatitis c virus: a long-term follow-up. J Hepatol 2017;66:S23.
45. Kobayashi M, Suzuki F, Fujiyama S, Kawamura Y, Sezaki H, et al. Sustained virologic response by direct antiviral agents reduces the incidence of hepatocellular carcinoma in patients with HCV infection. J Med Virol 2017;89:476-83.
46. Nagata H, Nakagawa M, Asahina Y, Sato A, Asano Y, et al. Effect of interferon-based and -free therapy on early occurrence and recurrence of hepatocellular carcinoma in chronic hepatitis C. J Hepatol 2017;67:933-9.
47. Affronti A, Ju M, Catt J, Rosenberg WM, Macdonald D. Successful hepatitis C treatment in advanced cirrhosis with DAA reduces HCC incidence. Hepatology 2016;64:475A.
48. Bielen R, Moreno C, Van Vlierberghe H, Bourgeois S, Mulkay JP, et al. The risk of early occurrence and recurrence of hepatocellular carcinoma in hepatitis C-infected patients treated with direct-acting antivirals with and without pegylated interferon: a Belgian experience. J Viral Hepat 2017;24:976-81.
49. Ioannou GN, Green PK, Berry K. HCV eradication induced by direct-acting antiviral agents reduces the risk of hepatocellular carcinoma. J Hepatol 2017; doi: 10.1016/j.jhep.2017.08.030.
50. Kozbial K, Moser S, Schwarzer R, Laferl H, Al-Zoairy 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;65:856-8.
51. Cardoso H, Vale AM, Rodrigues S, Gonçalves R, Albuquerque A, et al. High incidence of hepatocellular carcinoma following successful interferon-free antiviral therapy for hepatitis C associated cirrhosis. J Hepatol 2016;65:1070-1.
52. Singer AW, Reddy KR, Telep LE, Osinusi AO, Brainard DM, et al. Direct-acting antiviral treatment for hepatitis C virus infection and risk of incident liver cancer: a retrospective cohort study. Aliment Pharmacol Ther 2018;47:1278-87.
53. Li DK, Ren Y, Fierer DS, Rutledge S, Shaikh OS, et al. The short-term incidence of hepatocellular carcinoma is not increased after hepatitis C treatment with direct-acting antivirals: an ERCHIVES study. Hepatology 2018;67:2244-53.
54. Bruix J, Takayama T, Mazzaferro V, Chau GY, Yang J, et al. Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol 2015;16:1344-54.
55. Cammà C, Cabibbo G, Craxì A. Direct antiviral agents and risk for HCC early recurrence: much ado about nothing. J Hepatol 2016;65:861-2.
56. 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;65:734-40.
57. Zavaglia C, Okolicsanyi S, Cesarini L, Mazzarelli C, Pontecorvi V, et al. Is the risk of neoplastic recurrence increased after prescribing direct-acting antivirals for HCV patients whose HCC was previously cured? J Hepatol 2017;66:236-7.
58. Cabibbo G, Petta S, Calvaruso V, Cacciola I, Cannavò MR, et al. Is early recurrence of hepatocellular carcinoma in HCV cirrhotic patients affected by treatment with direct-acting antivirals? A prospective multicentre study. Aliment Pharmacol Ther 2017;46:688-95.
59. Petta S, Cabibbo G, Barbara M, Attardo S, Bucci L, et al. Hepatocellular carcinoma recurrence in patients with curative resection or ablation: impact of HCV eradication does not depend on the use of interferon. Aliment Pharmacol Ther 2017;45:160-8.
60. Kolly P, Waidmann O, Vermehren J, Moreno C, Vögeli I, et al. Hepatocellular carcinoma recurrence after direct antiviral agent treatment: a European multicentre study. J Hepatol 2017;67:876-8.
61. Waziry R, Hajarizadeh B, Grebely J, Amin J, Law M, et al. Hepatocellular carcinoma risk following direct-acting antiviral HCV therapy: a systematic review, meta-analyses, and meta-regression. J Hepatol 2017;67:1204-12.
62. Saraiya N, Yopp AC, Rich NE, Odewole M, Parikh ND, et al. Systematic review with meta-analysis: recurrence of hepatocellular carcinoma following direct-acting antiviral therapy. Aliment Pharmacol Ther 2018;48:127-37.
63. Nakao Y, Hashimoto S, Abiru S, Komori A, Yamasaki K, et al. Rapidly growing, moderately differentiated HCC: a clinicopathological characteristic of HCC occurrence after IFN-free DAA therapy? J Hepatol 2017; doi: 10.1016/j.jhep.2017.11.011.
64. Renzulli M, Buonfiglioli F, Conti F, Brocchi S, Serio I, et al. Imaging features of microvascular invasion in hepatocellular carcinoma developed after direct-acting antiviral therapy in HCV-related cirrhosis. Eur Radiol 2018;28:506-13.
65. Nahon P, Bourcier V, Layese R, Audureau E, Cagnot C, et al. Eradication of hepatitis C virus infection in patients with cirrhosis reduces risk of liver and non-liver complications. Gastroenterology 2017;152:142-56.
66. Zanetto A, Shalaby S, Vitale A, Mescoli C, Ferrarese A, et al. Dropout rate from the liver transplant waiting list because of hepatocellular carcinoma progression in hepatitis C virus-infected patients treated with direct-acting antivirals. Liver Transpl 2017;23:1103-12.
67. Werner JM, Adenugba A, Protzer U. Immune reconstitution after HCV clearance with direct antiviral agents: potential consequences for patients with HCC? Transplantation 2017;101:904-9.
68. Claassen MA, Janssen HL, Boonstra A. Role of T cell immunity in hepatitis C virus infections. Curr Opin Virol 2013;3:461-7.
69. Burchill MA, Golden-Mason L, Wind-Rotolo M, Rosen HR. Memory re-differentiation and reduced lymphocyte activation in chronic HCV-infected patients receiving direct-acting antivirals. J Viral Hepat 2015;22:983-91.
70. Yoong KF, McNab G, Hübscher SG, Adams DH. Vascular adhesion protein-1 and ICAM-1 support the adhesion of tumor-infiltrating lymphocytes to tumor endothelium in human hepatocellular carcinoma. J Immunol 1998;160:3978-88.
71. Flecken T, Schmidt N, Hild S, Gostick E, Drognitz O, et al. Immunodominance and functional alterations of tumor-associated antigen-specific CD8+ T-cell responses in hepatocellular carcinoma. Hepatology 2014;59:1415-26.
72. Wada Y, Nakashima O, Kutami R, Yamamoto O, Kojiro M. Clinicopathological study on hepatocellular carcinoma with lymphocytic infiltration. Hepatology 1998;27:407-14.
73. Fu J, Xu D, Liu Z, Shi M, Zhao P, et al. Increased regulatory T cells correlate with CD8 T-cell impairment and poor survival in hepatocellular carcinoma patients. Gastroenterology 2007;132:2328-39.
74. Debes JD, Janssen HL, Boonstra A. Hepatitis C treatment and liver cancer recurrence: cause for concern? Lancet Gastroenterol Hepatol 2017;2:78-80.
75. Cerwenka A, Lanier LL. Natural killer cell memory in infection, inflammation and cancer. Nat Rev Immunol 2016;16:112-23.
76. Körner C, Riesner K, Krämer B, Eisenhardt M, Glässner A, et al. TRAIL receptor I (DR4) polymorphisms C626G and A683C are associated with an increased risk for hepatocellular carcinoma (HCC) in HCV-infected patients. BMC Cancer 2012;12:85.
77. Spaan M, van Oord G, Kreefft K, Hou J, Hansen BE, 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;213:216-23.
78. Serti E, Chepa-Lotrea X, Kim YJ, Keane M, Fryzek N, et al. Successful interferon-free therapy of chronic hepatitis C virus infection normalizes natural killer cell function. Gastroenterology 2015;149:190-200.
79. Waring JF, Dumas EO, Abel S, Coakley E, Cohen DE, et al. Serum miR-122 may serve as a biomarker for response to direct acting antivirals: effect of paritaprevir/R with dasabuvir or ombitasvir on miR-122 in HCV-infected subjects. J Viral Hepat 2016;23:96-104.
80. Tsai WC, Hsu PW, Lai TC, Chau GY, Lin CW, et al. MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma. Hepatology 2009;49:1571-82.
81. Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007;9:654-9.
82. Andersen CL, Jensen JL, Ørntoft TF. Normalization of real-time quantitative reverse transcription-PCR data: a model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets. Cancer Res 2004;64:5245-50.
83. Waidmann O, Bihrer V, Kronenberger B, Zeuzem S, Piiper A, et al. Pretreatment serum microRNA-122 is not predictive for treatment response in chronic hepatitis C virus infection. Dig Liver Dis 2012;44:438-41.
84. Villani R, Facciorusso A, Bellanti F, Tamborra R, Piscazzi A, et al. DAAs rapidly reduce inflammation but increase serum VEGF Level: a rationale for tumor risk during anti-hcv treatment. PLoS One 2016;11:e0167934.
85. Faillaci F, Marzi L, Critelli R, Milosa F, Schepis F, et al. Liver angiopoietin-2 is a key predictor of de novo or recurrent hepatocellular cancer after hepatitis C virus direct-acting antivirals. Hepatology 2018;68:1010-24.
86. Debes JD, van Tilborg M, Groothuismink ZMA, Hansen BE, Schulze Zur Wiesch J, et al. Levels of cytokines in serum associate with development of hepatocellular carcinoma in patients with HCV infection treated with direct-acting antivirals. Gastroenterology 2018;154:515-7.
87. Jühling F, Bandiera S, Hamdane N, Thumann C, Durand SC, et al. Hepatitis C virus-induced epigenetic and transcriptional changes persist post cure. J Hepatol 2017;66:S21.
89. Pinato DJ, Stebbing J, Ishizuka M, Khan SA, Wasan HS, et al. A novel and validated prognostic index in hepatocellular carcinoma: the inflammation based index (IBI). J Hepatol 2012;57:1013-20.
90. Pinato DJ, Sharma R, Allara E, Yen C, Arizumi T, et al. The ALBI grade provides objective hepatic reserve estimation across each BCLC stage of hepatocellular carcinoma. J Hepatol 2017;66:338-46.
91. Casadei Gardini A, Scarpi E, Faloppi L, Scartozzi M, Silvestris N, Santini D, et al. Immune inflammation indicators and implication for immune modulation strategies in advanced hepatocellular carcinoma patients receiving sorafenib. Oncotarget 2016;7:67142-9.
92. Casadei Gardini A, Foschi FG, Conti F, Petracci E, Vukotic R, et al. Immune inflammation indicators and ALBI score to predict liver cancer in HCV-patients treated with direct-acting antivirals. Dig Liver Dis 2018; doi: 10.1016/j.dld.2018.09.016.
93. European Association for the Study of the Liver. Electronic address:
94. Majumdar A, Kitson MT, Roberts SK. Systematic review: current concepts and challenges for the direct-acting antiviral era in hepatitis C cirrhosis. Aliment Pharmacol Ther 2016;43:1276-92.
95. Toniutto P, Zanetto A, Ferrarese A, Burra P. Current challenges and future directions for liver transplantation. Liver Int 2017;37:317-27.
96. Zeng QL, Li ZQ, Liang HX, Xu GH, Li CX, et al. Unexpected high incidence of hepatocellular carcinoma in patients with hepatitis C in the era of DAAs: too alarming? J Hepatol 2016;65:1068-9.
97. Carrat F. Clinical outcomes in HCV-infected patients treated with direct acting antivirals - 18-month post-treatment follow-up in the French ANRS CO22 HEPATHER Cohort study. J Hepatol 2016;64:S215.
98. Innes H, Barclay ST, Hayes PC, Fraser A, Dillon JF, et al. Among cirrhotic patients with a hepatitis C sustained viral response, the risk of de-novo hepatocellular carcinoma relates to baseline factors and not the use of direct acting antivirals: results from a nationwide cohort. J Hepatol 2017;66:S22-3.
99. Calvaruso V, Cabibbo G, Cacciola I, Petta S, Madonia S, et al. Occurrence of hepatocellular carcinoma in patients with hepatitis C virus related liver disease treated with direct-acting antivirals. J Hepatol 2017;66:S23-4.
100. Issachar A, Sneh-Arbib O, Braun M, Shlomai A, Oxtrud E, et al. Occurrence and recurrence of malignancies post DAA Treatment in 5.1% of patients- single center experience. J Hepatol 2017;66:S97.
101. Kanwal F, Kramer J, Asch SM, Chayanupatkul M, Cao Y, et al. Risk of hepatocellular cancer in HCV patients treated with direct-acting antiviral agents. Gastroenterology 2017;153:996-1005.e1.
102. Ogata F, Kobayashi M, Akuta N, Osawa M, Fujiyama S, et al. Outcome of all-oral direct-acting antiviral regimens on the rate of development of hepatocellular carcinoma in patients with hepatitis C virus genotype 1-related chronic liver disease. Oncology 2017;93:92-8.
103. Deterding K, Mauss S, Pathil A, Buggisch P, Schott E, et al. Long-term follow-up after IFN-free therapy of advanced HCV-associated liver cirrhosis: continued improvement of liver function parameters – results from the German hepatitis C-registry (DHC-R). J Hepatol 2017;66:S55.
104. Finkelmeier F, Dultz G, Peiffer KH, Kronenberger B, Krauss F, et al. Risk of de novo hepatocellular carcinoma after HCV treatment with direct-acting antivirals. Liver Cancer 2018;7:190-204.
