Effect of achieving sustained virological response before hepatitis C virus-related hepatocellular carcinoma occurrence on survival and recurrence after curative surgical microwave ablation
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Background and aim
The effects of achieving sustained virological response (SVR) on recurrence and survival after curative treatment in patients with hepatitis virus C (HCV)-related hepatocellular carcinoma (HCC) is unclear. This study examined the influence of SVR achievement by interferon therapy before HCC occurrence on recurrence and survival.
This retrospective study included 518 patients who underwent surgical microwave ablation for initial HCV-related HCC between January 2001 and December 2015. Thirty-four patients had achieved SVR (SVR group) and 484 patients had not (control group). Clinical characteristics and long-term outcomes were compared between the two groups.
Overall survival rates at 5 and 10 years after curative ablation were 95.8 and 80.4% in the SVR group, and 50.7 and 23.4% in the control, respectively (p < 0.0001). Recurrence-free survival rates at 5 and 10 years were 68.7 and 26.4% in the SVR group, and 24.5 and 7.8% in the control group, respectively (p < 0.0001). Multivariate analyses revealed that achieving SVR as an independent prognostic factor for both overall and recurrence-free survival. In the SVR group, the 5-year recurrence-free survival rates for patients with an interval of 5 years or fewer (n = 24) vs. more than 5 years (n = 10) between achieving SVR and curative ablation were 58.7 and 88.9%, respectively (p = 0.03).
Achieving SVR before HCC occurrence allowed a favorable clinical outcome after curative ablation in HCV-related HCC patients. Patients with HCC that occurred more than 5 years after achieving SVR had longer recurrence-free survival.
KeywordsHepatitis C Sustained virological response Microwave ablation Hepatocellular carcinoma Interferon
Study conception and design: TR, YT, and HS. Acquisition of data: TR, YW, MT, HM, MY, and KM. Analysis and interpretation of data: TR, YT, and HS. Drafting of manuscript: TR. Critical revision: YT, and HS.
Compliance with ethical standards
Conflict of interest
Tomoki Ryu, Yuko Takami, Yoshiyuki Wada, Masaki Tateishi, Hajime Matsushima, Munehiro Yoshitomi, Kazuhiro Mikagi, and Hideki Saitsu declare that they have no conflicts of interest.
- 1.Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 2006;24:2137–2150.Google Scholar
- 2.Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet 2003;362:1907–1917.Google Scholar
- 3.Umemura T, Ichijo T, Yoshizawa K, Tanaka E, Kiyosawa K. Epidemiology of hepatocellular carcinoma in Japan. J Gastroenterol 2009;44:102–107.Google Scholar
- 4.Llovet JM, Schwartz M, Mazzaferro V. Resection and liver transplantation for hepatocellular carcinoma. Semin Liver Dis 2005;25:181–200.Google Scholar
- 5.International Interferon-alpha Hepatocellular Carcinoma Study Group. Effect of interferon-alpha on progression of cirrhosis to hepatocellular carcinoma: a retrospective cohort study. Lancet 1998;351:1535–1539.Google Scholar
- 6.Ikeda K, Saitoh S, Arase Y, Chayama K, Suzuki Y, Kobayashi M, Tsubota A, Kobayashi M, Nakamura I, Murashima N, Kumada H, Kawanishi M. 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;29:1124–1130.Google Scholar
- 7.Okanoue T, Itoh Y, Minami M, Sakamoto S, Yasui K, Sakamoto M, Nishioji K, Murakami Y, Kashima K. Interferon therapy lowers the rate of progression to hepatocellular carcinoma in chronic hepatitis C but not significantly in an advanced stage: a retrospective study in 1148 patients. Viral Hepatitis Therapy Study Group. J Hepatol 1999;30:653–659.Google Scholar
- 8.Ikeda K, Arase Y, Saitoh S, Kobayashi M, Suzuki Y, Suzuki F, Tsubota A, Chayama K, Murashima N, Kumada H. Interferon beta prevents recurrence of hepatocellular carcinoma after complete resection or ablation of the primary tumor—a prospective randomized study of hepatitis C virus-related liver cancer. Hepatology 2000;32:228–232.Google Scholar
- 9.Mazzaferro V, Romito R, Schiavo M, Mariani L, Camerini T, Bhoori S, Capussotti L, Calise F, Pellicci R, Belli G, Tagger A, Colombo M, Bonino F, Majno P, Llovet JM. Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis. Hepatology 2006;44:1543–1554.Google Scholar
- 10.Kubo S, Nishiguchi S, Hirohashi K, Tanaka H, Tsukamoto T, Shuto T, Takemura S, Yamamoto T, Ikebe T, Wakasa K, Shiomi S, Kinoshia H. Influence of previous interferon therapy on recurrence after resection of hepatitis. Jpn J Cancer Res 2001;92:59–66.Google Scholar
- 11.Saito T, Chiba T, Suzuki E, Shinozaki M, Goto N, Kanogawa N, Motoyama T, Ogasawara S, Ooka Y, Tawada Y, Kanda T, Miyazaki M, Yokosuka O. Effect of previous interferon based therapy on recurrence after curative treatment of hepatitis C virus-related hepatocellular carcinoma. Int J Med Sci 2014;11:707–712.Google Scholar
- 12.Miyatake H, Kobayashi Y, Iwasaki Y, Nakamura S, Ohnishi H, Kuwaki K, Toshomori J, Hagihara H, Nouso K, Yamamoto K. Effect of previous interferon treatment on outcome after curative treatment for hepatitis C virus-related hepatocellular carcinoma. Dig Dis Sci 2012;57:1092–1101.Google Scholar
- 13.Kanogawa N, Ogasawara S, Chiba T, Saito T, Motoyama T, Suzuki E, Ooka Y, Tawada A, Kanda T, Mikami S, Azemoto R, Kaiho T, Shinozaki M, Ohtsuka M, Miyazaki M, Yokosuka O. Sustained virologic response achieved after curative treatment of hepatitis C virus-related hepatocellular carcinoma as an independent prognostic factor. J Gastroenterol Hepatol 2015;30:1197–1204.Google Scholar
- 14.Conti F, Buonfiglioli F, Scuteri A, Crepsi 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.Google Scholar
- 15.Takami Y, Ryu T, Wada Y, Saitsu H. Evaluation of intraoperative microwave coagulo-necrotic therapy (MCN) for hepatocellular carcinoma: a single center experience of 719 consecutive cases. J Hepatobiliary Pancreat Sci 2013;20:332–3341.Google Scholar
- 16.Ryu T, Takami Y, Tsutsumi N, Tateishi M, Mikagi K, Wada Y, Saitsu H. Simultaneous microwave coagulo-necrotic therapy (MCN) and laparoscopic splenectomy for the treatment of hepatocellular carcinoma with cirrhotic hypersplenism. Surg Today 2017;47:548–554.Google Scholar
- 17.Wada Y, Takami Y, Tateishi M, Ryu T, Mikagi K, Saitsu H. Efficacy of surgical treatment using microwave coagulo-necrotic therapy for unresectable multiple colorectal liver metastases. OncoTargets Ther 2016;9:937–943.Google Scholar
- 18.Takenaka K, Kawahara N, Yamamoto K, Kajiyama K, Maeda T, Itasaka H, Shirabe K, Nishizaki T, Yanaga K, Sugimachi K. Results of 280 liver resections for hepatocellular carcinoma. Arch Surg 1996;131:71–76.Google Scholar
- 19.Kobayashi A, Miyagawa S, Miwa S, Nakata T. Prognostic impact of anatomical resection on early and late intrahepatic recurrence in patients with hepatocellular carcinoma. J Hepatobiliary Pancreat Surg 2008;15:515–521.Google Scholar
- 20.Ikeda K, Arase Y, Kobayashi M, Saitoh S, Someya T, Hosaka T, Suzuki Y, Suzuki F, Tsubota A, Akuta N, Kumada H. Significance of multicentric cancer recurrence after potentially curative ablation of hepatocellular carcinoma: a longterm cohort study of 892 patients with viral cirrhosis. J Gastroenterol 2003;38:865–876.Google Scholar
- 21.Nagaoki Y, Aikata H, Nakano N, Shinohara F, Nakamura Y, Hatooka M, Morio K, Kan H, Fujino H, Kobayashi T, Fukuhara T, Masaki K, Ono A, Nakahara T, Kawaoka T, Miki D, Tsuge M, Hiramatsu A, Imamura M, Takahashi S, Kawakami Y, Ochi H, Chayama K. Development of hepatocellular carcinoma in patients with hepatitis C virus infection who achieved sustained virological response following interferon therapy: a large-scale, long-term cohort study. J Gastroenterol Hepatol 2016;31:1009–1015.Google Scholar
- 22.International Consensus Group for Hepatocellular Neoplasia. Pathologic diagnosis of early hepatocellular carcinoma: a report of the international consensus group for hepatocellular neoplasia. Hepatology 2009;49:658–664.Google Scholar