Skip to main content
Top
Published in: Annals of Surgical Oncology 13/2019

01-12-2019 | Hepatocellular Carcinoma | Hepatobiliary Tumors

The Achievement of a Sustained Virological Response Either Before or After Hepatectomy Improves the Prognosis of Patients with Primary Hepatitis C Virus-Related Hepatocellular Carcinoma

Authors: Yukiyasu Okamura, MD, Teiichi Sugiura, MD, Takaaki Ito, MD, Yusuke Yamamoto, MD, Ryo Ashida, MD, Katsuhisa Ohgi, MD, Katsuhiko Uesaka, MD

Published in: Annals of Surgical Oncology | Issue 13/2019

Login to get access

Abstract

Background

Hepatitis C virus (HCV) infection is a major cause of hepatocellular carcinoma (HCC). Achieving a sustained virological response (SVR) is associated with a reduced risk of recurrence. The recent introduction of direct acting antivirals (DAAs) has resulted in SVR rates of nearly 100% in treated patients. The purpose of the present study was to clarify the outcomes in patients who underwent antiviral therapy and patients without antiviral therapy.

Methods

This retrospective study included 220 patients with primary HCV-related HCC who underwent hepatectomy. An SVR was defined as a serum HCV-RNA titer below the detection sensitivity limit at 6 months after the termination of antiviral therapy. Postoperative antiviral therapy was introduced after confirming that there was no early recurrence.

Results

Eighty-eight patients received antiviral therapy. Among these, 58 patients (66%) obtained an SVR. With the exception of one patient, all patients who received DAAs obtained an SVR. The overall survival rate of the pre-operative SVR group was significantly better than that of the preoperative untreated group (P = 0.045). Moreover, there was no recurrence at 3 years after surgery in the pre-operative SVR group. The achievement of an SVR was an independent predictor of overall survival [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.59–0.94, P = 0.011] and recurrence (HR 0.61, 95% CI 0.40–0.94, P = 0.024).

Conclusions

Obtaining an SVR either before or after surgery was associated with the suppression of HCC recurrence after hepatectomy in patients with primary HCV-related HCC.
Literature
2.
go back to reference Kudo M, Izumi N, Sakamoto M, et al. Liver Cancer Study Group of Japan. Survival analysis over 28 years of 173,378 patients with hepatocellular carcinoma in Japan. Liver Cancer. 2016;5:190–7. Kudo M, Izumi N, Sakamoto M, et al. Liver Cancer Study Group of Japan. Survival analysis over 28 years of 173,378 patients with hepatocellular carcinoma in Japan. Liver Cancer. 2016;5:190–7.
3.
go back to reference Shim JH, Jun MJ, Han S, et al. Prognostic nomograms for prediction of recurrence and survival after curative liver resection for hepatocellular carcinoma. Ann Surg. 2015;261:939–46.CrossRef Shim JH, Jun MJ, Han S, et al. Prognostic nomograms for prediction of recurrence and survival after curative liver resection for hepatocellular carcinoma. Ann Surg. 2015;261:939–46.CrossRef
4.
go back to reference Chapman WC, Klintmalm G, Hemming A, et al. Surgical treatment of hepatocellular carcinoma in North America: can hepatic resection still be justified? J Am Coll Surg. 2015;220:628–37.CrossRef Chapman WC, Klintmalm G, Hemming A, et al. Surgical treatment of hepatocellular carcinoma in North America: can hepatic resection still be justified? J Am Coll Surg. 2015;220:628–37.CrossRef
5.
go back to reference Yamamoto T, Kajino K, Kudo M, Sasaki Y, Arakawa Y, Hino O. Determination of the clonal origin of multiple human hepatocellular carcinomas by cloning and polymerase chain reaction of the integrated hepatitis B virus DNA. Hepatology. 1999;29:1446–52.CrossRef Yamamoto T, Kajino K, Kudo M, Sasaki Y, Arakawa Y, Hino O. Determination of the clonal origin of multiple human hepatocellular carcinomas by cloning and polymerase chain reaction of the integrated hepatitis B virus DNA. Hepatology. 1999;29:1446–52.CrossRef
6.
go back to reference Yasui M, Harada A, Nonami T, et al. Potentially multicentric hepatocellular carcinoma: clinicopathologic characteristics and postoperative prognosis. World J Surg. 1997;21:860–4.CrossRef Yasui M, Harada A, Nonami T, et al. Potentially multicentric hepatocellular carcinoma: clinicopathologic characteristics and postoperative prognosis. World J Surg. 1997;21:860–4.CrossRef
7.
go back to reference Matsuda M, Fujii H, Kono H, Matsumoto Y. Surgical treatment of recurrent hepatocellular carcinoma based on the mode of recurrence: repeat hepatic resection or ablation are good choices for patients with recurrent multicentric cancer. J Hepatobiliary Pancreat Surg. 2001;8:353–9.CrossRef Matsuda M, Fujii H, Kono H, Matsumoto Y. Surgical treatment of recurrent hepatocellular carcinoma based on the mode of recurrence: repeat hepatic resection or ablation are good choices for patients with recurrent multicentric cancer. J Hepatobiliary Pancreat Surg. 2001;8:353–9.CrossRef
8.
go back to reference Arii S, Monden K, Niwano M, et al. Results of surgical treatment for recurrent hepatocellular carcinoma; comparison of outcome among patients with multicentric carcinogenesis, intrahepatic metastasis, and extrahepatic recurrence. J Hepatobiliary Pancreat Surg. 1998;5:86–92.CrossRef Arii S, Monden K, Niwano M, et al. Results of surgical treatment for recurrent hepatocellular carcinoma; comparison of outcome among patients with multicentric carcinogenesis, intrahepatic metastasis, and extrahepatic recurrence. J Hepatobiliary Pancreat Surg. 1998;5:86–92.CrossRef
9.
go back to reference Imamura H, Matsuyama Y, Tanaka E, et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol. 2003;38:200–7.CrossRef Imamura H, Matsuyama Y, Tanaka E, et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol. 2003;38:200–7.CrossRef
10.
go back to reference Mazzaferro V, Romito R, Schiavo M, et al. HCC Italian Task Force. Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis. Hepatology. 2006;44:1543–54. Mazzaferro V, Romito R, Schiavo M, et al. HCC Italian Task Force. Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis. Hepatology. 2006;44:1543–54.
11.
go back to reference Shinkawa H, Hasegawa K, Arita J, et al. Impact of sustained virological response to interferon therapy on recurrence of hepatitis C virus-related hepatocellular carcinoma. Ann Surg Oncol. 2017;24:3196–202.CrossRef Shinkawa H, Hasegawa K, Arita J, et al. Impact of sustained virological response to interferon therapy on recurrence of hepatitis C virus-related hepatocellular carcinoma. Ann Surg Oncol. 2017;24:3196–202.CrossRef
12.
go back to reference Koda M, Tanaka S, Takemura S, et al. Long-term prognostic factors after hepatic resection for hepatitis C virus-related hepatocellular carcinoma, with a special reference to viral status. Liver Cancer. 2018;7:261–76.CrossRef Koda M, Tanaka S, Takemura S, et al. Long-term prognostic factors after hepatic resection for hepatitis C virus-related hepatocellular carcinoma, with a special reference to viral status. Liver Cancer. 2018;7:261–76.CrossRef
13.
go back to reference 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;65:727–33.CrossRef 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;65:727–33.CrossRef
14.
go back to reference 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;65:719–26.CrossRef 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;65:719–26.CrossRef
15.
go back to reference Kozbial K, Moser S, Schwarzer R, et al. Unexpected high incidence of hepatocellular carcinoma in cirrhotic patients with sustained virologic response following interferon-free directacting antiviral treatment. J Hepatol. 2016;65:856–8.CrossRef Kozbial K, Moser S, Schwarzer R, et al. Unexpected high incidence of hepatocellular carcinoma in cirrhotic patients with sustained virologic response following interferon-free directacting antiviral treatment. J Hepatol. 2016;65:856–8.CrossRef
16.
go back to reference Cardoso H, Vale AM, Rodrigues S, et al. High incidence of hepatocellular carcinoma following successful interferon-free antiviral therapy for hepatitis C associated cirrhosis. J Hepatol. 2016;65:1070–1.CrossRef Cardoso H, Vale AM, Rodrigues S, et al. High incidence of hepatocellular carcinoma following successful interferon-free antiviral therapy for hepatitis C associated cirrhosis. J Hepatol. 2016;65:1070–1.CrossRef
17.
go back to reference 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. 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.
18.
go back to reference Torres HA, Vauthey JN, Economides MP, Mahale P, Kaseb A. Hepatocellular carcinoma recurrence after treatment with directacting antivirals: first, do no harm by withdrawing treatment. J Hepatol. 2016;65:862–4.CrossRef Torres HA, Vauthey JN, Economides MP, Mahale P, Kaseb A. Hepatocellular carcinoma recurrence after treatment with directacting antivirals: first, do no harm by withdrawing treatment. J Hepatol. 2016;65:862–4.CrossRef
19.
go back to reference Minami T, Tateishi R, Nakagomi R, et al. The impact of directacting antivirals on early tumor recurrence after radiofrequency ablation in hepatitis C-related hepatocellular carcinoma. J Hepatol. 2016;65:1272–3.CrossRef Minami T, Tateishi R, Nakagomi R, et al. The impact of directacting antivirals on early tumor recurrence after radiofrequency ablation in hepatitis C-related hepatocellular carcinoma. J Hepatol. 2016;65:1272–3.CrossRef
20.
go back to reference Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the esophagus for bleeding oesophageal varices. Br J Surg. 1973;60:646–9.CrossRef Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the esophagus for bleeding oesophageal varices. Br J Surg. 1973;60:646–9.CrossRef
21.
go back to reference Liver Cancer Study Group of Japan General rules for the clinical and pathological study of primary liver cancer, 2008. 5th Japanese ed. Tokyo: Kanehara; 2008. Liver Cancer Study Group of Japan General rules for the clinical and pathological study of primary liver cancer, 2008. 5th Japanese ed. Tokyo: Kanehara; 2008.
22.
go back to reference Sobin LH, Gospodarowicz MK, Wittekind CH, editors. TNM Classification of Malignant Tumours, 7th ed. New York: Wiley-Liss; 2009. Sobin LH, Gospodarowicz MK, Wittekind CH, editors. TNM Classification of Malignant Tumours, 7th ed. New York: Wiley-Liss; 2009.
23.
go back to reference Okamura Y, Ito T, Sugiura T, Mori K, Uesaka K. Anatomic versus nonanatomic hepatectomy for a solitary hepatocellular carcinoma: a case-controlled study with propensity score matching. J Gastrointest Surg. 2014;18:1994–2002.CrossRef Okamura Y, Ito T, Sugiura T, Mori K, Uesaka K. Anatomic versus nonanatomic hepatectomy for a solitary hepatocellular carcinoma: a case-controlled study with propensity score matching. J Gastrointest Surg. 2014;18:1994–2002.CrossRef
24.
go back to reference Strasberg SM. Nomenclature of hepatic anatomy and resections: a review of the Brisbane 2000 system. J Hepatobiliary Pancreat Surg. 2005;12:351–5.CrossRef Strasberg SM. Nomenclature of hepatic anatomy and resections: a review of the Brisbane 2000 system. J Hepatobiliary Pancreat Surg. 2005;12:351–5.CrossRef
25.
go back to reference Kumada T, Nakano S, Takeda I, et al. Patterns of recurrence after initial treatment in patients with small hepatocellular carcinoma. Hepatology. 1997;25:87–92.CrossRef Kumada T, Nakano S, Takeda I, et al. Patterns of recurrence after initial treatment in patients with small hepatocellular carcinoma. Hepatology. 1997;25:87–92.CrossRef
26.
go back to reference Poon RT, Fan ST, Ng IO, Lo CM, Liu CL, Wong J. Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma. Cancer. 2000;89:500–7.CrossRef Poon RT, Fan ST, Ng IO, Lo CM, Liu CL, Wong J. Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma. Cancer. 2000;89:500–7.CrossRef
27.
go back to reference Ikeda K, Arase Y, Saitoh S, et al. 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;32:228–32.CrossRef Ikeda K, Arase Y, Saitoh S, et al. 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;32:228–32.CrossRef
28.
go back to reference Ikeda K, Kawamura Y, Kobayashi M, et al. Direct-acting antivirals decreased tumor recurrence after initial treatment of hepatitis C virus-related hepatocellular carcinoma. Dig Dis Sci. 2017;62:2932–42.CrossRef Ikeda K, Kawamura Y, Kobayashi M, et al. Direct-acting antivirals decreased tumor recurrence after initial treatment of hepatitis C virus-related hepatocellular carcinoma. Dig Dis Sci. 2017;62:2932–42.CrossRef
Metadata
Title
The Achievement of a Sustained Virological Response Either Before or After Hepatectomy Improves the Prognosis of Patients with Primary Hepatitis C Virus-Related Hepatocellular Carcinoma
Authors
Yukiyasu Okamura, MD
Teiichi Sugiura, MD
Takaaki Ito, MD
Yusuke Yamamoto, MD
Ryo Ashida, MD
Katsuhisa Ohgi, MD
Katsuhiko Uesaka, MD
Publication date
01-12-2019
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 13/2019
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-019-07911-w

Other articles of this Issue 13/2019

Annals of Surgical Oncology 13/2019 Go to the issue