Highlights
- •Post-hepatectomy viral reactivation developed in 9.5% of HBV-infected patients with ICC.
- •Viral reactivation was associated with worse short- and long-term surgical outcomes.
- •Antiviral therapy initiated before surgery reduced the incidence of viral reactivation.
- •Antiviral therapy started either before or after surgery improved survival outcomes.
Background & Aims
The impact of hepatitis B virus (HBV) infection on outcomes after resection of intrahepatic
cholangiocarcinoma (ICC) has not been reported. The aim of this study was to examine
the impact of antiviral therapy on survival outcomes after liver resection for patients
with ICC and underlying HBV infection.
Methods
Data on 928 patients with ICC and HBV infection who underwent liver resection at two
medical centers between 2006 and 2011 were analyzed. Data on viral reactivation, tumor
recurrence, cancer-specific survival (CSS) and overall survival (OS) were obtained.
Survival rates were analyzed using the time-dependent Cox regression model adjusted
for potential covariates.
Results
Postoperative viral reactivation occurred in 3.3%, 8.3% and 15.7% of patients who
received preoperative antiviral therapy, who did not receive preoperative antiviral
therapy with a low, or a high HBV-DNA level (< or ≥2,000 IU/ml), respectively (p <0.001). A high viral level and viral reactivation were independent risk factors
of recurrence (hazard ratio [HR] 1.22 and 1.34), CSS (HR 1.36 and 1.46) and OS (HR 1.23 and 1.36). Five-year recurrence, CSS and OS were better in patients who received
antiviral therapy (70.5%, 46.9% and 43.0%) compared with patients who did not receive
antiviral therapy and had a high viral level (86.5%, 20.9% and 20.5%, all p <0.001), respectively. The differences in recurrence, CSS and OS were minimal compared
with no-antiviral therapy patients with a low viral level (71.7%, 35.5% and 33.5%,
p = 0.057, 0.051 and 0.060, respectively). Compared to patients with a high viral level
who received no antiviral therapy, patients who initiated antiviral therapy either
before or after surgery had better long-term outcomes (HR 0.44 and 0.54 for recurrence;
0.38 and 0.57 for CSS; 0.46 and 0.54 for OS, respectively).
Conclusions
Viral reactivation was associated with worse prognoses after liver resection for HBV-infected
patients with ICC. Antiviral therapy decreased viral reactivation and prolonged long-term
survival for patients with ICC and a high viral level.
Lay summary
Postoperative hepatitis B virus reactivation was associated with an increased complication
rate and a decreased survival rate after liver resection in patients with ICC and
hepatitis B virus infection. Antiviral therapy before liver resection reduced the
risk of postoperative viral reactivation. Both pre- and postoperative antiviral therapy
was effective in prolonging patient survival.
Graphical abstract

Graphical Abstract
Keywords
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References
Author names in bold designate shared co-first authorship
- Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma.J Hepatol. 2014; 60: 1268-1289
- Epidemiology, risk factors, and pathogenesis of cholangiocarcinoma.HPB. 2008; 10: 77-82
- Surgical management of intrahepatic cholangiocarcinoma–a population-based study.Ann Surg Oncol. 2008; 15: 600-608
- Intrahepatic cholangiocarcinoma: report of 272 patients compared with 5,829 patients with hepatocellular carcinoma.J Cancer Res Clin Oncol. 2009; 135: 1073-1080
- Prognostic nomogram for intrahepatic cholangiocarcinoma after partial hepatectomy.J Clin Oncol. 2013; 31: 1188-1195
- Results of surgical treatment for intrahepatic cholangiocarcinoma and clinicopathological factors influencing survival.Br J Surg. 2002; 89: 1525-1531
- Trends in survival after surgery for cholangiocarcinoma: a 30-year population-based SEER database analysis.J Gastrointest Surg. 2007; 11 ([Discussion 1496–1497]): 1488-1496
- Hepatitis B virus infection increases the risk of cholangiocarcinoma: a meta-analysis and systematic review.J Gastroenterol Hepatol. 2012; 27: 1561-1568
- Hepatitis viruses infection and risk of intrahepatic cholangiocarcinoma: evidence from a meta-analysis.BMC Cancer. 2012; 12: 289
- Risk factors for intrahepatic and extrahepatic cholangiocarcinoma: a hospital-based case-control study.Am J Gastroenterol. 2007; 102: 1016-1021
- HBV induced carcinogenesis.J Clin Virol. 2005; 34: S75-S78
- Expression of HBx protein in hepatitis B virus-infected intrahepatic cholangiocarcinoma.Hepatobiliary Pancreat Int. 2012; 11: 532-535
- Association between nucleoside analogues and risk of hepatitis B virus-related hepatocellular carcinoma recurrence following liver resection.JAMA. 2012; 308: 1906-1914
- Hepatitis B reactivation in patients with hepatocellular carcinoma undergoing systemic chemotherapy.Ann Oncol. 2004; 15: 1661-1666
- Perioperative reactivation of hepatitis B virus replication in patients undergoing partial hepatectomy for hepatocellular carcinoma.J Gastroenterol Hepatol. 2012; 27: 158-164
- Posthepatectomy HBV reactivation in hepatitis B-related hepatocellular carcinoma influences postoperative survival in patients with preoperative low HBV-DNA levels.Ann Surg. 2013; 257: 490-505
- Molecular diagnosis of intrahepatic cholangiocarcinoma.J Hepatobiliary Pancreat Sci. 2015; 22: 114-123
- WHO classification of tumours: pathology and genetics of tumours of the digestive system.IARC, Lyon, France2000
- WHO classification of tumours of the digestive system.IARC, Lyon, France2010
- Intrahepatic cholangiocarcinoma: new insights in pathology.Semin Liver Dis. 2011; 31: 49-60
- The impact of surgical margin status on long-term outcome after resection for intrahepatic cholangiocarcinoma.Ann Surg Oncol. 2015; 22: 4020-4028
- Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey.Ann Surg. 2004; 240: 205-213
- The “50-50 criteria” on postoperative day 5: an accurate predictor of liver failure and death after hepatectomy.Ann Surg. 2005; 242: 824-829
- Asian-Pacific consensus statement on the management of chronic hepatitis B: an update.J Gastroenterol Hepatol. 2003; 18: 239-245
- EASL Clinical Practice Guidelines: management of chronic hepatitis B.J Hepatol. 2009; 50: 227-242
- Risk factors for early and late recurrence in hepatitis B-related hepatocellular carcinoma.J Hepatol. 2009; 51: 890-897
- Comparison of entecavir and lamivudine in preventing hepatitis B reactivation in lymphoma patients during chemotherapy.J Viral Hepat. 2011; 18: 877-883
- Hepatitis B reactivation after withdrawal of pre-emptive lamivudine in patients with haematological malignancy on completion of cytotoxic chemotherapy.Gut. 2005; 54: 1597-1603
- Randomized controlled trial of entecavir prophylaxis for rituximab-associated hepatitis B virus reactivation in patients with lymphoma and resolved hepatitis B.J Clin Oncol. 2013; 31: 2765-2772
- Reactivation of hepatitis B.Hepatology. 2009; 49: S156-S165
- Perioperative blood transfusion in hepatocellular carcinomas: influence of immunologic profile and recurrence free survival.Cancer. 2001; 91: 771-778
- Morphological subclassification of intrahepatic cholangiocarcinoma: etiological, clinicopathological, and molecular features.Mod Pathol. 2014; 27: 1163-1173
- Viral hepatitis is associated with intrahepatic cholangiocarcinoma with cholangiolar differentiation and N-cadherin expression.Mod Pathol. 2011; 24: 810-819
- Chronic hepatitis B: update 2009.Hepatology. 2009; 50: 661-662
Article info
Publication history
Published online: November 16, 2017
Accepted:
November 1,
2017
Received in revised form:
October 19,
2017
Received:
April 26,
2017
Identification
Copyright
© 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.