Skip to main content
Top
Published in: BMC Gastroenterology 1/2019

Open Access 01-12-2019 | Hepatitis B | Research article

Prior hepatitis B virus infection as a co-factor of chronic hepatitis C patient survival after resection of hepatocellular carcinoma

Authors: Yutaka Midorikawa, Tadatoshi Takayama, Hisashi Nakayama, Tokio Higaki, Masamichi Moriguchi, Kyoji Moriya, Tatsuo Kanda, Shunichi Matsuoka, Mitsuhiko Moriyama

Published in: BMC Gastroenterology | Issue 1/2019

Login to get access

Abstract

Background

Prior hepatitis B virus infection (PBI) may increase the risk of developing hepatocellular carcinoma (HCC), but the impact of PBI on clinical outcomes following treatment for HCC remains unknown. The aim of this study was to clarify whether PBI affects clinical outcomes after liver resection for hepatitis C virus (HCV)-related HCC by retrospective cohort study.

Methods

PBI patients were defined as those negative for hepatitis B surface antigen and positive for anti-hepatitis B core antibody. Surgical outcomes of HCV-related HCC patients with PBI were compared to those without PBI. Survival of patients with non-B non-C HCC with and without PBI were also compared.

Results

In the HCV group, the median overall survival of 165 patients with PBI was 4.7 years (95% confidence interval [CI], 3.9–5.9), and was significantly shorter compared with 263 patients without PBI (6.6 years [5.3–9.8]; p = 0.015). Conversely, there was no significant difference in recurrence-free survival between the two groups (1.8 years [95% CI, 1.4–2.0] vs 2.0 years [1.7–2.3]; p = 0.205). On Cox proportional hazards regression model, independent factors for overall survival were PBI (hazard ratio 1.38 [95% CI, 1.02–1.87]; p = 0.033), multiple tumors (p = 0.007), tumor size (p = 0.002), and liver cirrhosis (p <  0.001). On the other hand, in the non-B non-C HCC group, both the median overall survival (6.5 years [95% CI, 4.8–7.1]) and recurrence-free survival (2.4 years, [95% CI, 1.5–3.3]) in 104 patients with PBI were not significantly different from those (7.5 years [5.5 − NA; p = 0.932]; and 2.2 years [1.7–2.7; p = 0.983]) in 213 patients without PBI.

Conclusions

PBI and HCV in conjunction with each other affect the survival of patients that have undergone resection for HCC.
Literature
1.
go back to reference Raimondo G, Allain JP, Brunetto MR, Buendia MA, Chen DS, Colombo M, et al. Statements from the Taormina expert meeting on occult hepatitis B virus infection. J Hepatol. 2008;49:652–7.CrossRef Raimondo G, Allain JP, Brunetto MR, Buendia MA, Chen DS, Colombo M, et al. Statements from the Taormina expert meeting on occult hepatitis B virus infection. J Hepatol. 2008;49:652–7.CrossRef
2.
go back to reference Matsuzaki Y, Sato M, Saito Y, Karube M, Doy M, Shoda J, et al. The role of previous infection of hepatitis B virus in Hbs antigen negative and anti-HCV negative Japanese patients with hepatocellular carcinoma: etiological and molecular biological study. J Exp Clin Cancer Res. 1999;18:379–89.PubMed Matsuzaki Y, Sato M, Saito Y, Karube M, Doy M, Shoda J, et al. The role of previous infection of hepatitis B virus in Hbs antigen negative and anti-HCV negative Japanese patients with hepatocellular carcinoma: etiological and molecular biological study. J Exp Clin Cancer Res. 1999;18:379–89.PubMed
3.
go back to reference Tamori A, Nishiguchi S, Kubo S, Narimatsu T, Habu D, Takeda T, et al. HBV DNA integration and HBV-transcript expression in non-B, non-C hepatocellular carcinoma in Japan. J Med Virol. 2003;71:492–8.CrossRef Tamori A, Nishiguchi S, Kubo S, Narimatsu T, Habu D, Takeda T, et al. HBV DNA integration and HBV-transcript expression in non-B, non-C hepatocellular carcinoma in Japan. J Med Virol. 2003;71:492–8.CrossRef
4.
go back to reference Adachi S, Shibuya A, Miura Y, Takeuchi A, Nakazawa T, Saigenji K. Impact of occult hepatitis B virus infection and prior hepatitis B virus infection on development of hepatocellular carcinoma in patients with liver cirrhosis due to hepatitis C virus. Scand J Gastroenterol. 2008;43:849–56.CrossRef Adachi S, Shibuya A, Miura Y, Takeuchi A, Nakazawa T, Saigenji K. Impact of occult hepatitis B virus infection and prior hepatitis B virus infection on development of hepatocellular carcinoma in patients with liver cirrhosis due to hepatitis C virus. Scand J Gastroenterol. 2008;43:849–56.CrossRef
5.
go back to reference Giannini E, Ceppa P, Botta F, Fasoli A, Romagnoli P, Ansaldi F, et al. Previous hepatitis B virus infection is associated with worse disease stage and occult hepatitis B virus infection has low prevalence and pathogenicity in hepatitis C virus-positive patients. Liver Int. 2003;23:12–8.CrossRef Giannini E, Ceppa P, Botta F, Fasoli A, Romagnoli P, Ansaldi F, et al. Previous hepatitis B virus infection is associated with worse disease stage and occult hepatitis B virus infection has low prevalence and pathogenicity in hepatitis C virus-positive patients. Liver Int. 2003;23:12–8.CrossRef
6.
go back to reference Kubo S, Tamori A, Ohba K, Shuto T, Yamamoto T, Tanaka H, et al. Previous or occult hepatitis B virus infection in hepatitis C virus-associated hepatocellular carcinoma without hepatic fibrosis. Dig Dis Sci. 2001;46:2408–14.CrossRef Kubo S, Tamori A, Ohba K, Shuto T, Yamamoto T, Tanaka H, et al. Previous or occult hepatitis B virus infection in hepatitis C virus-associated hepatocellular carcinoma without hepatic fibrosis. Dig Dis Sci. 2001;46:2408–14.CrossRef
7.
go back to reference Sagnelli E, Coppola N, Scolastico C, Filippini P, Santantonio T, Stroffolini T, et al. Virologic and clinical expressions of reciprocal inhibitory effect of hepatitis B, C, and delta viruses in patients with chronic hepatitis. Hepatology. 2000;32:1106–10.CrossRef Sagnelli E, Coppola N, Scolastico C, Filippini P, Santantonio T, Stroffolini T, et al. Virologic and clinical expressions of reciprocal inhibitory effect of hepatitis B, C, and delta viruses in patients with chronic hepatitis. Hepatology. 2000;32:1106–10.CrossRef
8.
go back to reference Ikeda K, Marusawa H, Osaki Y, Nakamura T, Kitajima N, Yamashita Y, et al. Antibody to hepatitis B core antigen and risk for hepatitis C-related hepatocellular carcinoma: a prospective study. Ann Intern Med. 2007;146:649–56.CrossRef Ikeda K, Marusawa H, Osaki Y, Nakamura T, Kitajima N, Yamashita Y, et al. Antibody to hepatitis B core antigen and risk for hepatitis C-related hepatocellular carcinoma: a prospective study. Ann Intern Med. 2007;146:649–56.CrossRef
9.
go back to reference Squadrito G, Cacciola I, Alibrandi A, Pollicino T, Raimondo G. Impact of occult hepatitis B virus infection on the outcome of chronic hepatitis C. J Hepatol. 2013;59:696–700.CrossRef Squadrito G, Cacciola I, Alibrandi A, Pollicino T, Raimondo G. Impact of occult hepatitis B virus infection on the outcome of chronic hepatitis C. J Hepatol. 2013;59:696–700.CrossRef
10.
go back to reference Helmy A, Al-Sebayel MI. Isolated antibody to hepatitis B core antigen in patients with chronic hepatitis C virus infection. World J Gastroenterol. 2006;12:4406–10.CrossRef Helmy A, Al-Sebayel MI. Isolated antibody to hepatitis B core antigen in patients with chronic hepatitis C virus infection. World J Gastroenterol. 2006;12:4406–10.CrossRef
11.
go back to reference Levast M, Larrat S, Thelu MA, Nicod S, Plages A, Cheveau A, et al. Prevalence and impact of occult hepatitis B infection in chronic hepatitis C patients treated with pegylated interferon and ribavirin. J Med Virol. 2010;82:747–54.CrossRef Levast M, Larrat S, Thelu MA, Nicod S, Plages A, Cheveau A, et al. Prevalence and impact of occult hepatitis B infection in chronic hepatitis C patients treated with pegylated interferon and ribavirin. J Med Virol. 2010;82:747–54.CrossRef
12.
go back to reference Bruno S, Crosignani A, Maisonneuve P, Rossi S, Silini E, Mondelli MU. Hepatitis C virus genotype 1b as a major risk factor associated with hepatocellular carcinoma in patients with cirrhosis: a seventeen-year prospective cohort study. Hepatology. 2007;46:1350–6.CrossRef Bruno S, Crosignani A, Maisonneuve P, Rossi S, Silini E, Mondelli MU. Hepatitis C virus genotype 1b as a major risk factor associated with hepatocellular carcinoma in patients with cirrhosis: a seventeen-year prospective cohort study. Hepatology. 2007;46:1350–6.CrossRef
13.
go back to reference Hasegawa I, Orito E, Tanaka Y, Hirashima N, Sakakibara K, Sakurai M, et al. Impact of occult hepatitis B virus infection on efficacy and prognosis of interferon-alpha therapy for patients with chronic hepatitis C. Liver Int. 2005;25:247–53.CrossRef Hasegawa I, Orito E, Tanaka Y, Hirashima N, Sakakibara K, Sakurai M, et al. Impact of occult hepatitis B virus infection on efficacy and prognosis of interferon-alpha therapy for patients with chronic hepatitis C. Liver Int. 2005;25:247–53.CrossRef
14.
go back to reference Lok AS, Everhart JE, Di Bisceglie AM, Kim HY, Hussain M, Morgan TR, et al. Occult and previous hepatitis B virus infection are not associated with hepatocellular carcinoma in United States patients with chronic hepatitis C. Hepatology. 2011;54:434–42.CrossRef Lok AS, Everhart JE, Di Bisceglie AM, Kim HY, Hussain M, Morgan TR, et al. Occult and previous hepatitis B virus infection are not associated with hepatocellular carcinoma in United States patients with chronic hepatitis C. Hepatology. 2011;54:434–42.CrossRef
15.
go back to reference Itoh S, Yoshizumi T, Tomino T, Nagatsu A, Motomura T, Harada N, et al. Associations between antibody to hepatitis B core antigen positivity and outcomes in hepatocellular carcinoma patients undergoing hepatic resection. Hepatol Res. 2017;48:E155–61.CrossRef Itoh S, Yoshizumi T, Tomino T, Nagatsu A, Motomura T, Harada N, et al. Associations between antibody to hepatitis B core antigen positivity and outcomes in hepatocellular carcinoma patients undergoing hepatic resection. Hepatol Res. 2017;48:E155–61.CrossRef
16.
go back to reference Wu ZF, Xu Z, Li WS, Zhang HB, Yang N, Yao XQ, et al. Impact of occult hepatitis B virus infection on outcome after resection for non-B non-C hepatocellular carcinoma. J Surg Res. 2015;193:153–60.CrossRef Wu ZF, Xu Z, Li WS, Zhang HB, Yang N, Yao XQ, et al. Impact of occult hepatitis B virus infection on outcome after resection for non-B non-C hepatocellular carcinoma. J Surg Res. 2015;193:153–60.CrossRef
17.
go back to reference Coppola N, Onorato L, Pisaturo M, Macera M, Sagnelli C, Martini S, et al. Role of occult hepatitis B virus infection in chronic hepatitis C. World J Gastroenterol. 2015;21:11931–40.CrossRef Coppola N, Onorato L, Pisaturo M, Macera M, Sagnelli C, Martini S, et al. Role of occult hepatitis B virus infection in chronic hepatitis C. World J Gastroenterol. 2015;21:11931–40.CrossRef
18.
go back to reference Hui CK, Sun J, Au WY, Lie AK, Yueng YH, Zhang HY, et al. Occult hepatitis B virus infection in hematopoietic stem cell donors in a hepatitis B virus endemic area. J Hepatol. 2005;42:813–9.CrossRef Hui CK, Sun J, Au WY, Lie AK, Yueng YH, Zhang HY, et al. Occult hepatitis B virus infection in hematopoietic stem cell donors in a hepatitis B virus endemic area. J Hepatol. 2005;42:813–9.CrossRef
19.
go back to reference Nakamoto S, Kanda T, Nakaseko C, Sakaida E, Ohwada C, Takeuchi M, et al. Reactivation of hepatitis B virus in hematopoietic stem cell transplant recipients in Japan: efficacy of nucleos(t) ide analogues for prevention and treatment. Int J Mol Sci. 2014;15:21455–67.CrossRef Nakamoto S, Kanda T, Nakaseko C, Sakaida E, Ohwada C, Takeuchi M, et al. Reactivation of hepatitis B virus in hematopoietic stem cell transplant recipients in Japan: efficacy of nucleos(t) ide analogues for prevention and treatment. Int J Mol Sci. 2014;15:21455–67.CrossRef
20.
go back to reference Yeo W, Chan TC, Leung NW, Lam WY, Mo FK, Chu MT, et al. Hepatitis B virus reactivation in lymphoma patients with prior resolved hepatitis B undergoing anticancer therapy with or without rituximab. J Clin Oncol. 2009;27:605–11.CrossRef Yeo W, Chan TC, Leung NW, Lam WY, Mo FK, Chu MT, et al. Hepatitis B virus reactivation in lymphoma patients with prior resolved hepatitis B undergoing anticancer therapy with or without rituximab. J Clin Oncol. 2009;27:605–11.CrossRef
21.
go back to reference Raimondo G, Pollicino T, Cacciola I, Squadrito G. Occult hepatitis B virus infection. J Hepatol. 2007;46:160–70.CrossRef Raimondo G, Pollicino T, Cacciola I, Squadrito G. Occult hepatitis B virus infection. J Hepatol. 2007;46:160–70.CrossRef
22.
go back to reference El-Sherif A, Abou-Shady M, Abou-Zeid H, Elwassief A, Elbahrawy A, Ueda Y, et al. Antibody to hepatitis B core antigen as a screening test for occult hepatitis B virus infection in Egyptian chronic hepatitis C patients. J Gastroenterol. 2009;44:359–64.CrossRef El-Sherif A, Abou-Shady M, Abou-Zeid H, Elwassief A, Elbahrawy A, Ueda Y, et al. Antibody to hepatitis B core antigen as a screening test for occult hepatitis B virus infection in Egyptian chronic hepatitis C patients. J Gastroenterol. 2009;44:359–64.CrossRef
23.
go back to reference Urbani S, Fagnoni F, Missale G, Franchini M. The role of anti-core antibody response in the detection of occult hepatitis B virus infection. Clin Chem Lab Med. 2010;48:23–9.CrossRef Urbani S, Fagnoni F, Missale G, Franchini M. The role of anti-core antibody response in the detection of occult hepatitis B virus infection. Clin Chem Lab Med. 2010;48:23–9.CrossRef
24.
go back to reference Kokudo N, Hasegawa K, Akahane M, Igaki H, Izumi N, Ichida T, et al. Evidence-based clinical practice guidelines for hepatocellular carcinoma: the Japan Society of Hepatology 2013 update (3rd JSH-HCC guidelines). Hepatol Res. 2015;45:123–7.CrossRef Kokudo N, Hasegawa K, Akahane M, Igaki H, Izumi N, Ichida T, et al. Evidence-based clinical practice guidelines for hepatocellular carcinoma: the Japan Society of Hepatology 2013 update (3rd JSH-HCC guidelines). Hepatol Res. 2015;45:123–7.CrossRef
25.
go back to reference Makuuchi M, Kosuge T, Takayama T, Yamazaki S, Kakazu T, Miyagawa S, et al. Surgery for small liver cancers. Semin Surg Oncol. 1993;9:298–304.CrossRef Makuuchi M, Kosuge T, Takayama T, Yamazaki S, Kakazu T, Miyagawa S, et al. Surgery for small liver cancers. Semin Surg Oncol. 1993;9:298–304.CrossRef
26.
go back to reference Yamazaki S, Takayama T, Nakamura M, Higaki T, Matsuoka S, Mizuno S, et al. Prophylactic impact of endoscopic treatment for esophageal varices in liver resection: a prospective study. J Gastroenterol. 2014;49:917–22.CrossRef Yamazaki S, Takayama T, Nakamura M, Higaki T, Matsuoka S, Mizuno S, et al. Prophylactic impact of endoscopic treatment for esophageal varices in liver resection: a prospective study. J Gastroenterol. 2014;49:917–22.CrossRef
27.
go back to reference Takayama T, Makuuchi M, Kubota K, Harihara Y, Hui AM, Sano K, et al. Randomized comparison of ultrasonic vs clamp transection of the liver. Arch Surg. 2001;136:922–8.CrossRef Takayama T, Makuuchi M, Kubota K, Harihara Y, Hui AM, Sano K, et al. Randomized comparison of ultrasonic vs clamp transection of the liver. Arch Surg. 2001;136:922–8.CrossRef
28.
go back to reference Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205–13.CrossRef Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205–13.CrossRef
29.
go back to reference Midorikawa Y, Kubota K, Takayama T, Toyoda H, Ijichi M, Torzilli G, et al. A comparative study of postoperative complications after hepatectomy in patients with and without chronic liver disease. Surgery. 1999;126:484–91.CrossRef Midorikawa Y, Kubota K, Takayama T, Toyoda H, Ijichi M, Torzilli G, et al. A comparative study of postoperative complications after hepatectomy in patients with and without chronic liver disease. Surgery. 1999;126:484–91.CrossRef
30.
go back to reference Midorikawa Y, Takayama T, Shimada K, Nakayama H, Higaki T, Moriguchi M, et al. Marginal survival benefit in the treatment of early hepatocellular carcinoma. J Hepatol. 2013;58:306–11.CrossRef Midorikawa Y, Takayama T, Shimada K, Nakayama H, Higaki T, Moriguchi M, et al. Marginal survival benefit in the treatment of early hepatocellular carcinoma. J Hepatol. 2013;58:306–11.CrossRef
31.
go back to reference Raimondo G, Pollicino T, Squadrito G. What is the clinical impact of occult hepatitis B virus infection? Lancet. 2005;365:638–40.CrossRef Raimondo G, Pollicino T, Squadrito G. What is the clinical impact of occult hepatitis B virus infection? Lancet. 2005;365:638–40.CrossRef
32.
go back to reference Vento S, di Perri G, Luzzati R, Garofano T, Concia E, Bassetti D. Clinical reactivation of hepatitis B in anti-HBs-positive patients with AIDS. Lancet. 1989;1:332–3.CrossRef Vento S, di Perri G, Luzzati R, Garofano T, Concia E, Bassetti D. Clinical reactivation of hepatitis B in anti-HBs-positive patients with AIDS. Lancet. 1989;1:332–3.CrossRef
Metadata
Title
Prior hepatitis B virus infection as a co-factor of chronic hepatitis C patient survival after resection of hepatocellular carcinoma
Authors
Yutaka Midorikawa
Tadatoshi Takayama
Hisashi Nakayama
Tokio Higaki
Masamichi Moriguchi
Kyoji Moriya
Tatsuo Kanda
Shunichi Matsuoka
Mitsuhiko Moriyama
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2019
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/s12876-019-1069-y

Other articles of this Issue 1/2019

BMC Gastroenterology 1/2019 Go to the issue