Digestive Diseases

Original Paper

Hepatocellular Carcinoma after Achievement of Sustained Viral Response with Daclatasvir and Asunaprevir in Patients with Chronic Hepatitis C Virus Infection

Ida H. · Hagiwara S. · Kono M. · Minami T. · Chishina H. · Arizumi T. · Takita M. · Yada N. · Minami Y. · Ueshima K. · Nishida N. · Kudo M.

Author affiliations

Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka-Sayama, Japan

Keywords: Direct-acting antiviralsHepatitis C virusHepatocellular carcinomaSustained viral response

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Dig Dis 2017;35:565-573
https://doi.org/10.1159/000480183

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: October 17, 2017
Issue release date: October 2017

Number of Print Pages: 9
Number of Figures: 3
Number of Tables: 9

ISSN: 0257-2753 (Print)
eISSN: 1421-9875 (Online)

For additional information: https://www.karger.com/DDI

Abstract

Background: Interferon-based antiviral therapies against hepatitis C virus (HCV) infection have been shown to reduce the incidence of hepatocellular carcinoma (HCC) in patients with sustained viral response (SVR). Recently, direct-acting antivirals (DAAs) have been proven to be much more effective in achieving SVR than interferon-based therapies. However, whether DAAs can efficiently prevent the occurrence of HCC after SVR remains controversial. To clarify this issue, we analyzed the clinical features of patients in whom HCC developed after achievement of SVR with DAAs for chronic HCV infection. Summary: Among patients who achieved SVR with daclatasvir and asunaprevir (n = 100), HCC developed in 17 patients (HCC group; n = 17) and did not develop in 83 patients (non-HCC group; n = 83) during a mean observation period of 15 months. A multivariate Cox proportional hazards analysis identified past history of HCC and male sex as significant risk factors for the emergence of HCC after DAAs. Sixteen cases with HCC after DAAs were in the very early or early stage (16/17, 94.1%), and one case was in the advanced stage (1/17, 5.9%) with portal venous tumor thrombus. Radiofrequency ablation and/or transarterial chemoembolization were performed in most cases as curative therapy (16/17, 94.1%). Key Messages: SVR by DAAs did not completely prevent the occurrence of HCC. However, even if HCC did develop after SVR, curative anticancer therapy was applicable in most cases.

© 2017 S. Karger AG, Basel



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References

  1. Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74-108.
  2. Donato F, Tagger A, Chiesa R, Ribero ML, Tomasoni V, Fasola M, Gelatti U, Portera G, Boffetta P, Nardi G: Hepatitis B and C virus infection, alcohol drinking, and hepatocellular carcinoma: a case-control study in Italy. Brescia HCC Study. Hepatology 1997;26:579-584.
  3. Kim SR, Kudo M, Hino O, Han KH, Chung YH, Lee HS; Organizing Committee of Japan-Korea Liver S: Epidemiology of hepatocellular carcinoma in Japan and Korea. A review. Oncology 2008;75(suppl 1):13-16.
  4. Ahmad W, Ijaz B, Javed FT, Gull S, Kausar H, Sarwar MT, Asad S, Shahid I, Sumrin A, Khaliq S, Jahan S, Pervaiz A, Hassan S: A comparison of four fibrosis indexes in chronic HCV: development of new fibrosis-cirrhosis index (FCI). BMC Gastroenterol 2011;11:44.
  5. Chen SL, Morgan TR: The natural history of hepatitis C virus (HCV) infection. Int J Med Sci 2006;3:47-52.
  6. Kudo M: Surveillance, diagnosis, treatment, and outcome of liver cancer in Japan. Liver Cancer 2015;4:39-50.
  7. Kudo M: Clinical practice guidelines for hepatocellular carcinoma differ between Japan, United States, and Europe. Liver Cancer 2015;4:85-95.
  8. Hsu C, Chen BB, Chen CH, Ho MC, Cheng JC, Kokudo N, Murakami T, Yeo W, Seong J, Jia JD, Han KH, Cheng AL: Consensus development from the 5th Asia-Pacific primary liver cancer expert meeting (APPLE 2014). Liver Cancer 2015;4:96-105.
  9. Ichikawa S, Ichikawa T, Motosugi U, Sano K, Morisaka H, Enomoto N, Matsuda M, Fujii H: Was hypervascular hepatocellular carcinoma visible on previous gadoxetic acid-enhanced magnetic resonance images? Liver Cancer 2015;4:154-162.
  10. Chen BB, Murakami T, Shih TT, Sakamoto M, Matsui O, Choi BI, Kim MJ, Lee JM, Yang RJ, Zeng MS, Chen RC, Liang JD: Novel imaging diagnosis for hepatocellular carcinoma: consensus from the 5th Asia-Pacific primary liver cancer expert meeting (APPLE 2014). Liver Cancer 2015;4:215-227.
  11. Kudo M: Breakthrough imaging in hepatocellular carcinoma. Liver Cancer 2016;5:47-54.
  12. Toyoda H, Kumada T, Tada T, Sone Y, Kaneoka Y, Maeda A: Tumor markers for hepatocellular carcinoma: simple and significant predictors of outcome in patients with HCC. Liver Cancer 2015;4:126-136.
  13. Kudo M: Risk of hepatocellular carcinoma in patients with hepatitis C virus who achieved sustained virological response. Liver Cancer 2016;5:155-161.
  14. Ho MC, Hasegawa K, Chen XP, Nagano H, Lee YJ, Chau GY, Zhou J, Wang CC, Choi YR, Poon RT, Kokudo N: Surgery for intermediate and advanced hepatocellular carcinoma: a consensus report from the 5th Asia-Pacific primary liver Cancer expert meeting (APPLE 2014). Liver Cancer 2016;5:245-256.
  15. Kudo M: Locoregional therapy for hepatocellular carcinoma. Liver Cancer 2015;4:163-164.
  16. Teng W, Liu KW, Lin CC, Jeng WJ, Chen WT, Sheen IS, Lin CY, Lin SM: Insufficient ablative margin determined by early computed tomography may predict the recurrence of hepatocellular carcinoma after radiofrequency ablation. Liver Cancer 2015;4:26-38.
  17. Kang TW, Rhim H: Recent advances in tumor ablation for hepatocellular carcinoma. Liver Cancer 2015;4:176-187.
  18. Lencioni R, de Baere T, Martin RC, Nutting CW, Narayanan G: Image-guided ablation of malignant liver tumors: recommendations for clinical validation of novel thermal and non-thermal technologies - a western perspective. Liver Cancer 2015;4:208-214.
  19. Lin CC, Cheng YT, Chen MW, Lin SM: The effectiveness of multiple electrode radiofrequency ablation in patients with hepatocellular carcinoma with lesions more than 3 cm in size and barcelona clinic liver cancer stage A to B2. Liver Cancer 2016;5:8-20.
  20. Tsurusaki M, Murakami T: Surgical and locoregional therapy of HCC: TACE. Liver Cancer 2015;4:165-175.
  21. Kitai S, Kudo M, Nishida N, Izumi N, Sakamoto M, Matsuyama Y, Ichida T, Nakashima O, Matsui O, Ku Y, Kokudo N, Makuuchi M; Liver Cancer Study Group of Japan: Survival benefit of locoregional treatment for hepatocellular carcinoma with advanced liver cirrhosis. Liver Cancer 2016;5:175-189.
  22. Kudo M, Izumi N, Sakamoto M, Matsuyama Y, Ichida T, Nakashima O, Matsui O, Ku Y, Kokudo N, Makuuchi M: Survival analysis over 28 years of 173,378 patients with hepatocellular carcinoma in Japan. Liver Cancer 2016;5:190-197.
  23. Obi S, Sato S, Kawai T: Current status of hepatic arterial infusion chemotherapy. Liver Cancer 2015;4:188-199.
  24. Lin CC, Hung CF, Chen WT, Lin SM: Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein thrombosis: impact of early response to 4 weeks of treatment. Liver Cancer 2015;4:228-240.
  25. Kudo M: Molecular targeted therapy for hepatocellular carcinoma: where are we now? Liver Cancer 2015;4:I-VII.
  26. Kudo M: Regorafenib as second-line systemic therapy may change the treatment strategy and management paradigm for hepatocellular carcinoma. Liver Cancer 2016;5:235-244.
  27. Kudo M: Immune checkpoint blockade in hepatocellular carcinoma. Liver Cancer 2015;4:201-207.
  28. Douglas DD, Rakela J, Lin HJ, Hollinger FB, Taswell HF, Czaja AJ, Gross JB, Anderson ML, Parent K, Fleming CR, et al: Randomized controlled trial of recombinant alpha-2a-interferon for chronic hepatitis C. Comparison of alanine aminotransferase normalization versus loss of HCV RNA and anti-HCV IgM. Dig Dis Sci 1993;38:601-607.
  29. Sjogren MH, Sjogren R Jr, Lyons MF, Ryan M, Santoro J, Smith C, Reddy KR, Bonkovsky H, Huntley B, Faris-Young S: Antiviral response of HCV genotype 1 to consensus interferon and ribavirin versus pegylated interferon and ribavirin. Dig Dis Sci 2007;52:1540-1547.
  30. van der Meer AJ, Veldt BJ, Feld JJ, Wedemeyer H, Dufour JF, Lammert F, Duarte-Rojo A, Heathcote EJ, Manns MP, Kuske L, Zeuzem S, Hofmann WP, de Knegt RJ, Hansen BE, Janssen HL: Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA 2012;308:2584-2593.
  31. Mulhall BP, Younossi Z: Impact of adherence on the outcome of antiviral therapy for chronic hepatitis C. J Clin Gastroenterol 2005;39:S23-S27.
  32. Kumada H, Suzuki Y, Ikeda K, Toyota J, Karino Y, Chayama K, Kawakami Y, Ido A, Yamamoto K, Takaguchi K, Izumi N, Koike K, Takehara T, Kawada N, Sata M, Miyagoshi H, Eley T, McPhee F, Damokosh A, Ishikawa H, Hughes E: Daclatasvir plus asunaprevir for chronic HCV genotype 1b infection. Hepatology 2014;59:2083-2091.
  33. Mizokami M, Yokosuka O, Takehara T, Sakamoto N, Korenaga M, Mochizuki H, Nakane K, Enomoto H, Ikeda F, Yanase M, Toyoda H, Genda T, Umemura T, Yatsuhashi H, Ide T, Toda N, Nirei K, Ueno Y, Nishigaki Y, Betular J, Gao B, Ishizaki A, Omote M, Mo H, Garrison K, Pang PS, Knox SJ, Symonds WT, McHutchison JG, Izumi N, Omata M: Ledipasvir and sofosbuvir fixed-dose combination with and without ribavirin for 12 weeks in treatment-naive and previously treated Japanese patients with genotype 1 hepatitis C: an open-label, randomised, phase 3 trial. Lancet Infect Dis 2015;15:645-653.
  34. Nishida N, Goel A: Genetic and epigenetic signatures in human hepatocellular carcinoma: a systematic review. Curr Genomics 2011;12:130-137.
  35. Ciesek S, Manns MP: Hepatitis in 2010: the dawn of a new era in HCV therapy. Nat Rev Gastroenterol Hepatol 2011;8:69-71.
  36. Furusyo N, Ogawa E, Nakamuta M, Kajiwara E, Nomura H, Dohmen K, Takahashi K, Satoh T, Azuma K, Kawano A, Tanabe Y, Kotoh K, Shimoda S, Hayashi J; Kyushu University Liver Disease Study (KULDS) Group: Telaprevir can be successfully and safely used to treat older patients with genotype 1b chronic hepatitis C. J Hepatol 2013;59:205-212.
  37. Izumi N, Hayashi N, Kumada H, Okanoue T, Tsubouchi H, Yatsuhashi H, Kato M, Ki R, Komada Y, Seto C, Goto S: Once-daily simeprevir with peginterferon and ribavirin for treatment-experienced HCV genotype 1-infected patients in Japan: the CONCERTO-2 and CONCERTO-3 studies. J Gastroenterol 2014;49:941-953.
  38. Slim J, Afridi MS: Managing adverse effects of interferon-alfa and ribavirin in combination therapy for HCV. Infect Dis Clin North Am 2012;26:917-929.
  39. Chayama K, Takahashi S, Toyota J, Karino Y, Ikeda K, Ishikawa H, Watanabe H, McPhee F, Hughes E, Kumada H: Dual therapy with the nonstructural protein 5A inhibitor, daclatasvir, and the nonstructural protein 3 protease inhibitor, asunaprevir, in hepatitis C virus genotype 1b-infected null responders. Hepatology 2012;55:742-748.
  40. McPhee F, Suzuki Y, Toyota J, Karino Y, Chayama K, Kawakami Y, Yu ML, Ahn SH, Ishikawa H, Bhore R, Zhou N, Hernandez D, Mendez P, Kumada H: High sustained virologic response to daclatasvir plus asunaprevir in elderly and cirrhotic patients with hepatitis C virus genotype 1b without baseline NS5A polymorphisms. Adv Ther 2015;32:637-649.
  41. Serti E, Chepa-Lotrea X, Kim YJ, Keane M, Fryzek N, Liang TJ, Ghany M, Rehermann B: Successful interferon-free therapy of chronic hepatitis C virus infection normalizes natural killer cell function. Gastroenterology 2015;149:190-200.e2.
  42. Reig M, Marino Z, Perello C, Inarrairaegui M, Ribeiro A, Lens S, Diaz A, Vilana R, Darnell A, Varela M, Sangro B, Calleja JL, Forns X, Bruix J: Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy. J Hepatol 2016;65:719-726.
  43. Conti F, Buonfiglioli F, Scuteri A, Crespi C, Bolondi L, Caraceni P, Foschi FG, Lenzi M, Mazzella G, Verucchi G, Andreone P, Brillanti S: Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals. J Hepatol 2016;65:727-733.
  44. Kobayashi M, Suzuki F, Fujiyama S, Kawamura Y, Sezaki H, Hosaka T, Akuta N, Suzuki Y, Saitoh S, Arase Y, Ikeda K, Kumada H: Sustained virologic response by direct antiviral agents reduces the incidence of hepatocellular carcinoma in patients with HCV infection. J Med Virol 2017;89:476-483.
  45. Nagata H, Nakagawa M, Asahina Y, Sato A, Asano Y, Tsunoda T, Miyoshi M, Kaneko S, Otani S, Kawai-Kitahata F, Murakawa M, Nitta S, Itsui Y, Azuma S, Kakinuma S, Nouchi T, Sakai H, Tomita M, Watanabe M, Ochanomizu Liver Conference Study G: Effect of interferon-based and -free therapy on early occurrence and recurrence of hepatocellular carcinoma in chronic hepatitis C. J Hepatol 2017, pii: S0168-8278(17)32070-6.
  46. Chen MF, Liaw YF, Chen MF: Alpha fetoprotein and hepatic regeneration. Gastroenterology 1979;76:660.
  47. Asahina Y, Tsuchiya K, Nishimura T, Muraoka M, Suzuki Y, Tamaki N, Yasui Y, Hosokawa T, Ueda K, Nakanishi H, Itakura J, Takahashi Y, Kurosaki M, Enomoto N, Nakagawa M, Kakinuma S, Watanabe M, Izumi N: α-fetoprotein levels after interferon therapy and risk of hepatocarcinogenesis in chronic hepatitis C. Hepatology 2013;58:1253-1262.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: October 17, 2017
Issue release date: October 2017

Number of Print Pages: 9
Number of Figures: 3
Number of Tables: 9

ISSN: 0257-2753 (Print)
eISSN: 1421-9875 (Online)

For additional information: https://www.karger.com/DDI

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