Hepatocellular carcinoma risk following direct-acting antiviral HCV therapy: A systematic review, meta-analyses, and meta-regression

Journal of Hepatology

Volumn 67, Issue 6, 2017, Pages 1204-1212

  Waziry, Reem ^a   Hajarizadeh, Behzad ^a   Grebely, Jason ^a   Amin, Janaki ^b   Law, Matthew ^a   Danta, Mark ^c   George, Jacob ^d   Dore, Gregory J ^a  

^a UNIVERSITY OF NEW SOUTH WALES   (Australia)

^b MACQUARIE UNIVERSITY   (Australia)

^c UNIVERSITY OF NEW SOUTH WALES   (Australia)

^d UNIVERSITY OF SYDNEY   (Australia)

Author keywords

Chronic hepatitis C virus; Epidemiology; Hepatocellular carcinoma; Occurrence; Recurrence

Indexed keywords

ALPHA FETOPROTEIN; ANTIVIRUS AGENT; INTERFERON;

ANTIVIRAL THERAPY; ARTICLE; ASIA; CANCER INCIDENCE; CANCER RISK; EUROPE; FOLLOW UP; GEOGRAPHIC DISTRIBUTION; HEPATITIS C; HUMAN; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; META ANALYSIS; NORTH AMERICA; PRIORITY JOURNAL; RECURRENCE RISK; RECURRENT DISEASE; RISK ASSESSMENT; SYSTEMATIC REVIEW; AGED; CHRONIC HEPATITIS C; COMPLICATION; FEMALE; LIVER TUMOR; MALE; MIDDLE AGED; RISK; VIROLOGY;

AGED; ANTIVIRAL AGENTS; CARCINOMA, HEPATOCELLULAR; FEMALE; HEPATITIS C, CHRONIC; HUMANS; INTERFERONS; LIVER NEOPLASMS; MALE; MIDDLE AGED; RISK;

EID: 85029561799     PISSN: 01688278     EISSN: 16000641     Source Type: Journal    
DOI: 10.1016/j.jhep.2017.07.025     Document Type: Article

References (72)

1. Torre, L.A., Bray, F., Siegel, R.L., Ferlay, J., Lortet-Tieulent, J., Jemal, A., Global cancer statistics, 2012. CA Cancer J Clin 65 (2015), 87–108.
2. Abubakar, I., Tillmann, T., Banerjee, A., Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 385 (2015), 117–171.
3. Kanwal, F., Hoang, T., Kramer, J.R., Asch, S.M., Goetz, M.B., Zeringue, A., et al. Increasing prevalence of HCC and cirrhosis in patients with chronic hepatitis C virus infection. Gastroenterology 140 (2011), 1182–1188.
4. Wise, M., Bialek, S., Finelli, L., Bell, B.P., Sorvillo, F., Changing trends in hepatitis C–related mortality in the United States, 1995–2004. Hepatology 47 (2008), 1128–1135.
5. Belli, L.S., Berenguer, M., Cortesi, P.A., Strazzabosco, M., Rockenschaub, S.-R., Martini, S., et al. Delisting of liver transplant candidates with chronic hepatitis C after viral eradication: A European study. J Hepatol 65 (2016), 524–531.
6. Sievert, W., Razavi, H., Estes, C., Thompson, A.J., Zekry, A., Roberts, S.K., et al. Enhanced antiviral treatment efficacy and uptake in preventing the rising burden of hepatitis C-related liver disease and costs in Australia. J Gastroenterol Hepatol 29 (2014), 1–9.
7. Reig, M., Mariño, Z., Perelló, C., Iñarrairaegui, M., Ribeiro, A., Lens, S., et al. Unexpected early tumor recurrence in patients with hepatitis C virus-related hepatocellular carcinoma undergoing interferon-free therapy: a note of caution. J Hepatol 65 (2016), 719–726.
8. Pol, S., Lack of evidence of an effect of Direct Acting Antivirals on the recurrence of hepatocellular carcinoma: The ANRS collaborative study group on hepatocellular carcinoma (ANRS CO22 HEPATHER, CO12 CIRVIR and CO23 CUPILT cohorts). J Hepatol 65 (2016), 734–740.
9. Zeng, Q.-L., Li, Z.-Q., Liang, H.-X., Xu, G.-H., Li, C.-X., Zhang, D.-W., et al. Unexpected high incidence of hepatocellular carcinoma in patients with hepatitis C in the era of DAAs: Too alarming?. J Hepatol 65 (2016), 1068–1069.
10. Morgan, R.L., Baack, B., Smith, B.D., Yartel, A., Pitasi, M., Falck-Ytter, Y., Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: a meta-analysis of observational studies. Ann Intern Med 158 (2013), 329–337.
11. Morgan, T.R., Ghany, M.G., Kim, H.Y., Snow, K.K., Shiffman, M.L., De Santo, J.L., et al. Outcome of sustained virological responders with histologically advanced chronic hepatitis C. Hepatology 52 (2010), 833–844.
12. Nahon, P., Bourcier, V., Layese, R., Audureau, E., Cagnot, C., Marcellin, P., et al. Eradication of hepatitis C virus infection in patients with cirrhosis reduces risk of liver and non-liver complications. Gastroenterology 152 (2017), 142–156.
13. Brown Robert, S. Jr, The possible association between DAA treatment for HCV infection and HCC recurrence. Gastroenterol Hepatol, 12, 2016, 776.
14. Barbor M, Di Bisceglie AM. Can Antiviral Therapy Prevent Liver Cancer in Patients With Chronic Hepatitis? The ASCO Post 2017 [cited 2017 May 17]; Available from http://www.ascopost.com/issues/march-10-2017/can-antiviral-therapy-prevent-liver-cancer-in-patients-with-chronic-hepatitis/.
15. Llovet, J.M., Villanueva, A., Liver cancer: Effect of HCV clearance with direct-acting antiviral agents on HCC. Nature Rev Gastroenterol Hepatol 13 (2016), 561–562.
16. Marcellin, P., Estrabaud, E., Recent advances in hepatology. Liver Int 37 (2017), 3–6.
17. Nault, J.-C., Colombo, M., Hepatocellular carcinoma and direct acting antiviral treatments: Controversy after the revolution. J Hepatol 65 (2016), 663–665.
18. Wells G, Shea B, O'connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2008 [cited 2017 May]; Available from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm.
19. Higgins, J.P., Altman, D.G., Gøtzsche, P.C., Jüni, P., Moher, D., Oxman, A.D., et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ, 343, 2011, d5928.
20. Rothman, K., Greenland, S., Introduction to categorical statistics. Mod Epidemiol 3 (1998), 238–257.
21. Ioannidis, J.P., Patsopoulos, N.A., Evangelou, E., Uncertainty in heterogeneity estimates in meta-analyses. BMJ, 335, 2007, 914.
22. Ogawa, E., Furusyo, N., Kajiwara, E., Takahashi, K., Nomura, H., Maruyama, T., et al. Efficacy of pegylated interferon alpha-2b and ribavirin treatment on the risk of hepatocellular carcinoma in patients with chronic hepatitis C: a prospective, multicenter study. J Hepatol 58 (2013), 495–501.
23. D'Ambrosio, R., Aghemo, A., Rumi, M.G., Primignani, M., Dell'Era, A., Lampertico, P., et al. The course of esophageal varices in patients with hepatitis C cirrhosis responding to interferon/ribavirin therapy. Antivir Ther, 16, 2011, 677.
24. Cardoso, A.C., Moucari, R., Figueiredo-Mendes, C., Ripault, M.P., Giuily, N., Castelnau, C., et al. Impact of peginterferon and ribavirin therapy on hepatocellular carcinoma: incidence and survival in hepatitis C patients with advanced fibrosis. J Hepatol 52 (2010), 652–657.
25. Yu, M.L., Lin, S.M., Chuang, W.L., Dai, C.Y., Wang, J.H., Lu, S.N., et al. A sustained virological response to interferon or interferon/ribavirin reduces hepatocellular carcinoma and improves survival in chronic hepatitis C: a nationwide, multicentre study in Taiwan. Antivir Ther 11 (2006), 985–994.
26. Hung, C.H., Lee, C.M., Lu, S.N., Wang, J.H., Hu, T.H., Tung, H.D., et al. Long-term effect of interferon alpha-2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis. J Viral Hepat 13 (2006), 409–414.
27. Cheinquer, N., Cheinquer, H., Wolff, F.H., Coelho-Borges, S., Effect of sustained virologic response on the incidence of hepatocellular carcinoma in patients with HCV cirrhosis. Braz J Infect Dis 14 (2010), 457–461.
28. Moon, C., Jung, K.S., Kim, D.Y., Baatarkhuu, O., Park, J.Y., Kim, B.K., et al. Lower incidence of hepatocellular carcinoma and cirrhosis in hepatitis C patients with sustained virological response by pegylated interferon and ribavirin. Dig Dis Sci 60 (2015), 573–581.
29. Fernandez-Rodriguez, C.M., Alonso, S., Martinez, S.M., Forns, X., Sanchez-Tapias, J.M., Rincon, D., et al. Peginterferon plus ribavirin and sustained virological response in HCV-related cirrhosis: outcomes and factors predicting response. Am J Gastroenterol 105 (2010), 2164–2172.
30. Janjua, N.Z., Chong, M., Kuo, M., Woods, R., Wong, J., Yoshida, E.M., et al. Long-term effect of sustained virological response on hepatocellular carcinoma in patients with hepatitis C in Canada. J Hepatol 66 (2016), 504–513.
31. Rutter, K., Stattermayer, A.F., Beinhardt, S., Scherzer, T.M., Steindl-Munda, P., Trauner, M., et al. Successful anti-viral treatment improves survival of patients with advanced liver disease due to chronic hepatitis C. Aliment Pharmacol Ther 41 (2015), 521–531.
32. Velosa, J., Serejo, F., Marinho, R., Nunes, J., Gloria, H., Eradication of hepatitis C virus reduces the risk of hepatocellular carcinoma in patients with compensated cirrhosis. Dig Dis Sci 56 (2011), 1853–1861.
33. Aleman, S., Rahbin, N., Weiland, O., Davidsdottir, L., Hedenstierna, M., Rose, N., et al. A risk for hepatocellular carcinoma persists long-term after sustained virologic response in patients with hepatitis C-associated liver cirrhosis. Clin Infect Dis 57 (2013), 230–236.
34. Bruno, S., Zuin, M., Crosignani, A., Rossi, S., Zadra, F., Roffi, L., et al. Predicting mortality risk in patients with compensated HCV-induced cirrhosis: a long-term prospective study. Am J Gastroenterol 104 (2009), 1147–1158.
35. Mallet, V., Gilgenkrantz, H., Serpaggi, J., Verkarre, V., Vallet-Pichard, A., Fontaine, H., et al. Brief communication: the relationship of regression of cirrhosis to outcome in chronic hepatitis C. Ann Intern Med 149 (2008), 399–403.
36. Di Marco, V., Calvaruso, V., Ferraro, D., Bavetta, M.G., Cabibbo, G., Conte, E., et al. Effects of eradicating hepatitis C virus infection in patients with cirrhosis differ with stage of portal hypertension. Gastroenterology 151 (2016), 130–139.
37. Cardoso, H., Vale, A.M., Rodrigues, S., Gonçalves, R., Albuquerque, A., Pereira, P., et al. High incidence of hepatocellular carcinoma following successful interferon-free antiviral therapy for hepatitis C associated cirrhosis. J Hepatol 65 (2016), 1070–1071.
38. Conti, F., Buonfiglioli, F., Scuteri, A., Crespi, C., Bolondi, L., Caraceni, P., et al. Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct acting antivirals. J Hepatology 65 (2016), 727–733.
39. 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, 1, 2016, S215.
40. Affronti, A., Ju, M., Catt, J., Rosenberg, W.M., Macdonald, D., Successful hepatitis C treatment in advanced cirrhosis with DAA reduces HCC incidence. Hepatology 64 (2016), 475A–476A.
41. Muir, A.J., Buti, M., Nahass, R., Agarwal, K., Gane, E.J., Strasser, S.I., et al. Long-term follow-up of patients with chronic HCV infection and compensated or decompensated cirrhosis following treatment with sofosbuvir-based regimens. Hepatology, 2016, 437A–438A.
42. Romano, A., Capra, F., Piovesan, S., Chemello, L., Cavalletto, L., Anastassopoulos, G., et al. Incidence and pattern of“ de novo” hepatocellular carcinoma in HCV patients treated with oral DAAs. Hepatology, 64, 2016, 10A.
43. Kozbial, K., Moser, S., Schwarzer, R., Laferl, H., Al-Zoairy, R., Stauber, 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 65 (2016), 856–858.
44. Rinaldi, L., Di Francia, R., Coppola, N., Guerrera, B., Imparato, M., Monari, C., et al. Hepatocellular carcinoma in HCV cirrhosis after viral clearance with direct acting antiviral therapy: preliminary evidence and possible meanings. WCRJ, 3, 2016, e748.
45. Kunimoto, H., Ikeda, K., Sorin, Y., Fujiyama, S., Kawamura, Y., Kobayashi, M., et al. Long-term outcomes of hepatitis-C-infected patients achieving a sustained virological response and undergoing radical treatment for hepatocellular carcinoma. Oncology 90 (2016), 167–175.
46. Hagihara, H., Nouso, K., Kobayashi, Y., Iwasaki, Y., Nakamura, S., Kuwaki, K., et al. Effect of pegylated interferon therapy on intrahepatic recurrence after curative treatment of hepatitis C virus-related hepatocellular carcinoma. Int J Clin Oncol 16 (2011), 210–220.
47. Kanogawa, N., Ogasawara, S., Chiba, T., Saito, T., Motoyama, T., Suzuki, E., et al. Sustained virologic response achieved after curative treatment of hepatitis C virus-related hepatocellular carcinoma as an independent prognostic factor. J Gastroenterol Hepatol 30 (2015), 1197–1204.
48. Jeong, S.C., Aikata, H., Katamura, Y., Azakami, T., Kawaoka, T., Saneto, H., et al. Effects of a 24-week course of interferon-alpha therapy after curative treatment of hepatitis C virus-associated hepatocellular carcinoma. World J Gastroenterol, 13, 2007, 5343.
49. Saito, T., Chiba, T., Suzuki, E., Shinozaki, M., Goto, N., Kanogawa, N., et al. Effect of previous interferon-based therapy on recurrence after curative treatment of hepatitis C virus-related hepatocellular carcinoma. Int J Med Sci 11 (2014), 707–712.
50. Sanefuji, K., Kayashima, H., Iguchi, T., Sugimachi, K., Yamashita, Y., Yoshizumi, T., et al. Characterization of hepatocellular carcinoma developed after achieving sustained virological response to interferon therapy for hepatitis C. J Surg Oncol 99 (2009), 32–37.
51. Minami, T., Tateishi, R., Nakagomi, R., Fujiwara, N., Sato, M., Enooku, K., et al. The impact of direct-acting antivirals on early tumor recurrence after radiofrequency ablation in hepatitis C-related hepatocellular carcinoma. J Hepatol 65 (2016), 1272–1273.
52. Torres, H.A., Vauthey, J.-N., Economides, M.P., Mahale, P., Kaseb, A., Hepatocellular carcinoma recurrence after treatment with direct-acting antivirals: First, do no harm by withdrawing treatment. J Hepatol 65 (2016), 862–864.
53. Zavaglia, C., Okolicsanyi, S., Cesarini, L., Mazzarelli, C., Pontecorvi, V., Ciaccio, A., et al. Is the risk of neoplastic recurrence increased after prescribing direct-acting antivirals for HCV patients whose HCC was previously cured?. J Hepatol 66 (2016), 236–237.
54. Poordad, F., Hezode, C., Trinh, R., Kowdley, K.V., Zeuzem, S., Agarwal, K., et al. ABT-450/r–ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis. N Engl J Med 370 (2014), 1973–1982.
55. Poordad, F., Schiff, E.R., Vierling, J.M., Landis, C., Fontana, R.J., Yang, R., et al. Daclatasvir with sofosbuvir and ribavirin for hepatitis C virus infection with advanced cirrhosis or post-liver transplantation recurrence. Hepatology 63 (2016), 1493–1505.
56. Waziry, R., Grebely, J., Amin, J., Alavi, M., Hajarizadeh, B., George, J., et al. Trends in hepatocellular carcinoma among people with HBV or HCV notification in Australia (2000–2014). J Hepatol 65 (2016), 1086–1093.
57. El-Serag, H.B., Hepatocellular carcinoma: an epidemiologic view. J Clin Gastroenterol 35 (2002), S72–S78.
58. Mancebo, A., González-Diéguez, M.L., Navascués, C.A., Cadahía, V., Varela, M., Pérez, R., et al. Adherence to a semiannual surveillance program for hepatocellular carcinoma in patients with liver cirrhosis. J Clin Gastroenterol 51 (2017), 557–563.
59. Bruix, J., Sherman, M., Management of hepatocellular carcinoma: an update. Hepatology 53 (2011), 1020–1022.
60. Llovet, J.M., Brú, C., Bruix, J., Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis, 1999, 329–338.
61. Marubashi, S., Sakon, M., “Local recurrence” is not equal to “Local dissemination” after resection for hepatocellular carcinoma. J Hepatol, 65, 2016, 1061.
62. Knop, V., Hoppe, D., Welzel, T., Vermehren, J., Herrmann, E., Vermehren, A., et al. Regression of fibrosis and portal hypertension in HCV-associated cirrhosis and sustained virologic response after interferon-free antiviral therapy. J Viral Hepat 23 (2016), 994–1002.
63. Trottier B, Huchet E, Poliquin M, Bellon M, Vezina S, Galanakis C, et al. Fibrosis regression is possible after successful treatment of hepatitis C, even with cirrhosis. The 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention. Vancouver Convention Centre 19-22 July 2015.Available from: http://www.corevih-bretagne.fr/ckfinder/userfiles/files/Congr%C3%A8s/IAS_2015_Vancouver/IAS2015_Poster_Trottier.pdf.
64. S.O. Sekyere CF, A. Aregay, B. Schlevogt, K. Deterding,M.P. Manns, A. Vogel, T. Wirth, M. Cornberg, H. Wedemeyer. Interferon-free cure of hepatitis C virus infection does alter the soluble inflammatory milieu which could affect hepatocellular carcinoma surveillance by CD8+ T cells in patients with liver cirrhosis. International Liver Congress. Amsterdam. J Hepatol 2017;66:S1-S32.
65. Villani, R., Facciorusso, A., Bellanti, F., Tamborra, R., Piscazzi, A., Landriscina, M., et al. DAAs rapidly reduce inflammation but increase serum VEGF level: a rationale for tumor risk during anti-HCV treatment. PLoS One, 11, 2016, e0167934.
66. Lok, A.S., Seeff, L.B., Morgan, T.R., Di Bisceglie, A.M., Sterling, R.K., Curto, T.M., et al. Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease. Gastroenterology 136 (2009), 138–148.
67. Flemming, J.A., Kim, W., Brosgart, C.L., Terrault, N.A., Reduction in liver transplant wait-listing in the era of direct-acting antiviral therapy. Hepatology 65 (2016), 804–812.
68. Dore, G.J., Feld, J.J., Hepatitis C virus therapeutic development: in pursuit of “perfectovir”. Clin Infect Dis 60 (2015), 1829–1836.
69. Beste, L.A., Leipertz, S.L., Green, P.K., Dominitz, J.A., Ross, D., Ioannou, G.N., Trends in burden of cirrhosis and hepatocellular carcinoma by underlying liver disease in US veterans, 2001–2013. Gastroenterology 149 (2015), 1471–1482.
70. Vos, T., Flaxman, A.D., Naghavi, M., Lozano, R., Michaud, C., Ezzati, M., et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380 (2013), 2163–2196.
71. Scott, N., McBryde, E.S., Thompson, A., Doyle, J.S., Hellard, M.E., Treatment scale-up to achieve global HCV incidence and mortality elimination targets: a cost-effectiveness model. Gut, 311504, 2016.
72. Foster, G.R., Irving, W.L., Cheung, M.C., Walker, A.J., Hudson, B.E., Verma, S., et al. Impact of direct acting antiviral therapy in patients with chronic hepatitis C and decompensated cirrhosis. J Hepatol 64 (2016), 1224–1231.