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Published in: Annals of Surgical Oncology 12/2014

01-11-2014 | Hepatobiliary Tumors

Preoperative Aspartate Aminotransferase to Platelet Ratio is an Independent Prognostic Factor for Hepatitis B-Induced Hepatocellular Carcinoma After Hepatic Resection

Authors: Shun-Li Shen, MD, PhD, Shun-Jun Fu, MD, Bin Chen, MD, PhD, Ming Kuang, MD, PhD, Shao-Qiang Li, MD, PhD, Yun-Peng Hua, MD, PhD, Li-Jian Liang, MD, Pi Guo, MD, Yuantao Hao, MD, PhD, Bao-Gang Peng, MD, PhD

Published in: Annals of Surgical Oncology | Issue 12/2014

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Abstract

Background

There is conflicting evidence concerning platelet status and hepatocellular carcinoma (HCC) prognosis. We evaluated the prognostic value of platelet-based indices, including platelet count, platelet/lymphocyte ratio (PLR), and aspartate aminotransferase to platelet ratio index (APRI) in HCC after hepatic resection.

Methods

We retrospectively reviewed 332 patients with HCC treated with hepatectomy between 2006 and 2009. Preoperative platelet count, as well as demographic, clinical, and pathologic data, were analyzed.

Results

Both disease-free survival (DFS) and overall survival (OS) were significantly improved for patients with low platelet count, PLR, and APRI compared to patients with elevated values. On multivariate analysis, APRI, tumor size ≥5 cm, noncapsulation, and multiple tumors were all associated with both poor DFS and OS. The 1-, 3-, and 5-year DFS rates were 52, 36, and 32 % for patients with APRI <0.62 and were 35, 22, and 19 % for patients with APRI ≥0.62. Correspondingly, the 1-, 3-, and 5-year OS rates were 77, 51, and 42, and 63, 35, and 29 % for both groups. Both DFS and OS of patients with APRI <0.62 were significantly better compared to patients with an elevated APRI (P = 0.009 and 0.002, respectively). Patients with elevated APRI tended to have cirrhosis, hepatitis B virus (HBV) infection, surgical margin <1 cm, and noncapsulated tumors.

Conclusions

Elevated platelets based inflammatory indices, especially APRI, was associated with adverse characteristic features and poor prognosis in HCC, especially for patients with HBV infection or cirrhosis. Antiplatelet treatment may represent a potential therapy for HBV-induced HCC recurrence.
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Literature
1.
go back to reference Nguyen VT, Law MG, Dore GJ. Hepatitis B-related hepatocellular carcinoma: epidemiological characteristics and disease burden. J Viral Hepat. 2009;16:453–63.PubMedCrossRef Nguyen VT, Law MG, Dore GJ. Hepatitis B-related hepatocellular carcinoma: epidemiological characteristics and disease burden. J Viral Hepat. 2009;16:453–63.PubMedCrossRef
2.
go back to reference Ercolani G, Grazi GL, Ravaioli M, Del GM, Gardini A, Cescon M, et al. Liver resection for hepatocellular carcinoma on cirrhosis: univariate and multivariate analysis of risk factors for intrahepatic recurrence. Ann Surg. 2003;237:536–43.PubMedPubMedCentral Ercolani G, Grazi GL, Ravaioli M, Del GM, Gardini A, Cescon M, et al. Liver resection for hepatocellular carcinoma on cirrhosis: univariate and multivariate analysis of risk factors for intrahepatic recurrence. Ann Surg. 2003;237:536–43.PubMedPubMedCentral
4.
go back to reference Sasaki A, Iwashita Y, Shibata K, Matsumoto T, Ohta M, Kitano S. Prognostic value of preoperative peripheral blood monocyte count in patients with hepatocellular carcinoma. Surgery. 2006;139:755–64.PubMedCrossRef Sasaki A, Iwashita Y, Shibata K, Matsumoto T, Ohta M, Kitano S. Prognostic value of preoperative peripheral blood monocyte count in patients with hepatocellular carcinoma. Surgery. 2006;139:755–64.PubMedCrossRef
5.
go back to reference Gomez D, Farid S, Malik HZ, Young AL, Toogood GJ, Lodge JP, et al. Preoperative neutrophil-to-lymphocyte ratio as a prognostic predictor after curative resection for hepatocellular carcinoma. World J Surg. 2008;32:1757–62.PubMedCrossRef Gomez D, Farid S, Malik HZ, Young AL, Toogood GJ, Lodge JP, et al. Preoperative neutrophil-to-lymphocyte ratio as a prognostic predictor after curative resection for hepatocellular carcinoma. World J Surg. 2008;32:1757–62.PubMedCrossRef
6.
go back to reference Smith RA, Bosonnet L, Raraty M, Sutton R, Neoptolemos JP, Campbell F, et al. Preoperative platelet–lymphocyte ratio is an independent significant prognostic marker in resected pancreatic ductal adenocarcinoma. Am J Surg. 2009;197:466–72.PubMedCrossRef Smith RA, Bosonnet L, Raraty M, Sutton R, Neoptolemos JP, Campbell F, et al. Preoperative platelet–lymphocyte ratio is an independent significant prognostic marker in resected pancreatic ductal adenocarcinoma. Am J Surg. 2009;197:466–72.PubMedCrossRef
7.
go back to reference Sitia G, Aiolfi R, Di LP, Mainetti M, Fiocchi A, Mingozzi F, et al. Antiplatelet therapy prevents hepatocellular carcinoma and improves survival in a mouse model of chronic hepatitis B. Proc Natl Acad Sci USA. 2012;109:E2165–72.PubMedCrossRefPubMedCentral Sitia G, Aiolfi R, Di LP, Mainetti M, Fiocchi A, Mingozzi F, et al. Antiplatelet therapy prevents hepatocellular carcinoma and improves survival in a mouse model of chronic hepatitis B. Proc Natl Acad Sci USA. 2012;109:E2165–72.PubMedCrossRefPubMedCentral
8.
go back to reference Kurt M, Onal IK, Sayilir AY, Beyazit Y, Oztas E, Kekilli M, et al. The role of mean platelet volume in the diagnosis of hepatocellular carcinoma in patients with chronic liver disease. Hepatogastroenterology. 2012;59:1580–2.PubMed Kurt M, Onal IK, Sayilir AY, Beyazit Y, Oztas E, Kekilli M, et al. The role of mean platelet volume in the diagnosis of hepatocellular carcinoma in patients with chronic liver disease. Hepatogastroenterology. 2012;59:1580–2.PubMed
9.
go back to reference Maithel SK, Kneuertz PJ, Kooby DA, Scoggins CR, Weber SM, Martin RC II, et al. Importance of low preoperative platelet count in selecting patients for resection of hepatocellular carcinoma: a multi-institutional analysis. J Am Coll Surg. 2011;212:638–48.PubMedCrossRefPubMedCentral Maithel SK, Kneuertz PJ, Kooby DA, Scoggins CR, Weber SM, Martin RC II, et al. Importance of low preoperative platelet count in selecting patients for resection of hepatocellular carcinoma: a multi-institutional analysis. J Am Coll Surg. 2011;212:638–48.PubMedCrossRefPubMedCentral
10.
go back to reference Ichikawa T, Uenishi T, Takemura S, Oba K, Ogawa M, Kodai S, et al. A simple, noninvasively determined index predicting hepatic failure following liver resection for hepatocellular carcinoma. J Hepatobiliary Pancreat Surg. 2009;16:42–8.PubMedCrossRef Ichikawa T, Uenishi T, Takemura S, Oba K, Ogawa M, Kodai S, et al. A simple, noninvasively determined index predicting hepatic failure following liver resection for hepatocellular carcinoma. J Hepatobiliary Pancreat Surg. 2009;16:42–8.PubMedCrossRef
11.
go back to reference Amano H, Tashiro H, Oshita A, Kobayashi T, Tanimoto Y, Kuroda S, et al. Significance of platelet count in the outcomes of hepatectomized patients with hepatocellular carcinoma exceeding the Milan criteria. J Gastrointest Surg. 2011;15:1173–81.PubMedCrossRef Amano H, Tashiro H, Oshita A, Kobayashi T, Tanimoto Y, Kuroda S, et al. Significance of platelet count in the outcomes of hepatectomized patients with hepatocellular carcinoma exceeding the Milan criteria. J Gastrointest Surg. 2011;15:1173–81.PubMedCrossRef
12.
go back to reference Hwang SJ, Luo JC, Li CP, Chu CW, Wu JC, Lai CR, et al. Thrombocytosis: a paraneoplastic syndrome in patients with hepatocellular carcinoma. World J Gastroenterol. 2004;10:2472–7.PubMed Hwang SJ, Luo JC, Li CP, Chu CW, Wu JC, Lai CR, et al. Thrombocytosis: a paraneoplastic syndrome in patients with hepatocellular carcinoma. World J Gastroenterol. 2004;10:2472–7.PubMed
13.
go back to reference Gao J, Zhang HY, Xia YF. Increased platelet count is an indicator of metastasis in patients with nasopharyngeal carcinoma. Tumour Biol. 2013;34:39–45.PubMedCrossRef Gao J, Zhang HY, Xia YF. Increased platelet count is an indicator of metastasis in patients with nasopharyngeal carcinoma. Tumour Biol. 2013;34:39–45.PubMedCrossRef
14.
go back to reference Hwang SG, Kim KM, Cheong JH, Kim HI, An JY, Hyung WJ, et al. Impact of pretreatment thrombocytosis on blood-borne metastasis and prognosis of gastric cancer. Eur J Surg Oncol. 2012;38:562–7.PubMedCrossRef Hwang SG, Kim KM, Cheong JH, Kim HI, An JY, Hyung WJ, et al. Impact of pretreatment thrombocytosis on blood-borne metastasis and prognosis of gastric cancer. Eur J Surg Oncol. 2012;38:562–7.PubMedCrossRef
15.
go back to reference Fan J, Upadhye S, Worster A. Understanding receiver operating characteristic (ROC) curves. CJEM. 2006;8:19–20.PubMed Fan J, Upadhye S, Worster A. Understanding receiver operating characteristic (ROC) curves. CJEM. 2006;8:19–20.PubMed
16.
17.
18.
go back to reference Lin MS, Huang JX, Zhu J, Shen HZ. Elevation of platelet count in patients with colorectal cancer predicts tendency to metastases and poor prognosis. Hepatogastroenterology. 2012;59:1687–90.PubMed Lin MS, Huang JX, Zhu J, Shen HZ. Elevation of platelet count in patients with colorectal cancer predicts tendency to metastases and poor prognosis. Hepatogastroenterology. 2012;59:1687–90.PubMed
19.
go back to reference Gorelick C, Andikyan V, Mack M, Lee YC, Abulafia O. Prognostic significance of preoperative thrombocytosis in patients with endometrial carcinoma in an inner-city population. Int J Gynecol Cancer. 2009;19:1384–9.PubMedCrossRef Gorelick C, Andikyan V, Mack M, Lee YC, Abulafia O. Prognostic significance of preoperative thrombocytosis in patients with endometrial carcinoma in an inner-city population. Int J Gynecol Cancer. 2009;19:1384–9.PubMedCrossRef
20.
go back to reference Asher V, Lee J, Innamaa A, Bali A. Preoperative platelet lymphocyte ratio as an independent prognostic marker in ovarian cancer. Clin Transl Oncol. 2011;13:499–503.PubMedCrossRef Asher V, Lee J, Innamaa A, Bali A. Preoperative platelet lymphocyte ratio as an independent prognostic marker in ovarian cancer. Clin Transl Oncol. 2011;13:499–503.PubMedCrossRef
21.
go back to reference Raungkaewmanee S, Tangjitgamol S, Manusirivithaya S, Srijaipracharoen S, Thavaramara T. Platelet to lymphocyte ratio as a prognostic factor for epithelial ovarian cancer. J Gynecol Oncol. 2012;23:265–73.PubMedCrossRefPubMedCentral Raungkaewmanee S, Tangjitgamol S, Manusirivithaya S, Srijaipracharoen S, Thavaramara T. Platelet to lymphocyte ratio as a prognostic factor for epithelial ovarian cancer. J Gynecol Oncol. 2012;23:265–73.PubMedCrossRefPubMedCentral
22.
go back to reference Lin ZH, Xin YN, Dong QJ, Wang Q, Jiang XJ, Zhan SH, et al. Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis. Hepatology. 2011;53:726–36.PubMedCrossRef Lin ZH, Xin YN, Dong QJ, Wang Q, Jiang XJ, Zhan SH, et al. Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis. Hepatology. 2011;53:726–36.PubMedCrossRef
23.
go back to reference Hung HH, Su CW, Lai CR, Chau GY, Chan CC, Huang YH, et al. Fibrosis and AST to platelet ratio index predict post-operative prognosis for solitary small hepatitis B-related hepatocellular carcinoma. Hepatol Int. 2010;4:691–9.PubMedCrossRefPubMedCentral Hung HH, Su CW, Lai CR, Chau GY, Chan CC, Huang YH, et al. Fibrosis and AST to platelet ratio index predict post-operative prognosis for solitary small hepatitis B-related hepatocellular carcinoma. Hepatol Int. 2010;4:691–9.PubMedCrossRefPubMedCentral
24.
go back to reference Kao WY, Chiou YY, Hung HH, Chou YH, Su CW, Wu JC, et al. Risk factors for long-term prognosis in hepatocellular carcinoma after radiofrequency ablation therapy: the clinical implication of aspartate aminotransferase–platelet ratio index. Eur J Gastroenterol Hepatol. 2011;23:528–36.PubMed Kao WY, Chiou YY, Hung HH, Chou YH, Su CW, Wu JC, et al. Risk factors for long-term prognosis in hepatocellular carcinoma after radiofrequency ablation therapy: the clinical implication of aspartate aminotransferase–platelet ratio index. Eur J Gastroenterol Hepatol. 2011;23:528–36.PubMed
25.
go back to reference Sabrkhany S, Griffioen AW, Oude EMG. The role of blood platelets in tumor angiogenesis. Biochim Biophys Acta. 2011;1815:189–96.PubMed Sabrkhany S, Griffioen AW, Oude EMG. The role of blood platelets in tumor angiogenesis. Biochim Biophys Acta. 2011;1815:189–96.PubMed
27.
go back to reference Pinedo HM, Verheul HM, D’Amato RJ, Folkman J. Involvement of platelets in tumour angiogenesis. Lancet. 1998;352:1775–7.PubMedCrossRef Pinedo HM, Verheul HM, D’Amato RJ, Folkman J. Involvement of platelets in tumour angiogenesis. Lancet. 1998;352:1775–7.PubMedCrossRef
28.
30.
go back to reference Nieswandt B, Hafner M, Echtenacher B, Mannel DN. Lysis of tumor cells by natural killer cells in mice is impeded by platelets. Cancer Res. 1999;59:1295–300.PubMed Nieswandt B, Hafner M, Echtenacher B, Mannel DN. Lysis of tumor cells by natural killer cells in mice is impeded by platelets. Cancer Res. 1999;59:1295–300.PubMed
31.
go back to reference Choe KS, Correa D, Jani AB, Liauw SL. The use of anticoagulants improves biochemical control of localized prostate cancer treated with radiotherapy. Cancer. 2010;116:1820–6.PubMedCrossRef Choe KS, Correa D, Jani AB, Liauw SL. The use of anticoagulants improves biochemical control of localized prostate cancer treated with radiotherapy. Cancer. 2010;116:1820–6.PubMedCrossRef
32.
go back to reference Kuderer NM, Khorana AA, Lyman GH, Francis CW. A meta-analysis and systematic review of the efficacy and safety of anticoagulants as cancer treatment: impact on survival and bleeding complications. Cancer. 2007;110:1149–61.PubMedCrossRef Kuderer NM, Khorana AA, Lyman GH, Francis CW. A meta-analysis and systematic review of the efficacy and safety of anticoagulants as cancer treatment: impact on survival and bleeding complications. Cancer. 2007;110:1149–61.PubMedCrossRef
33.
go back to reference Klerk CP, Smorenburg SM, Otten HM, Lensing AW, Prins MH, Piovella F, et al. The effect of low molecular weight heparin on survival in patients with advanced malignancy. J Clin Oncol. 2005;23:2130–5.PubMedCrossRef Klerk CP, Smorenburg SM, Otten HM, Lensing AW, Prins MH, Piovella F, et al. The effect of low molecular weight heparin on survival in patients with advanced malignancy. J Clin Oncol. 2005;23:2130–5.PubMedCrossRef
34.
go back to reference van Doormaal FF, Di NM, Otten HM, Richel DJ, Prins M, Buller HR. Randomized trial of the effect of the low molecular weight heparin nadroparin on survival in patients with cancer. J Clin Oncol. 2011;29:2071–6.PubMedCrossRef van Doormaal FF, Di NM, Otten HM, Richel DJ, Prins M, Buller HR. Randomized trial of the effect of the low molecular weight heparin nadroparin on survival in patients with cancer. J Clin Oncol. 2011;29:2071–6.PubMedCrossRef
35.
go back to reference Iannacone M, Sitia G, Isogawa M, Marchese P, Castro MG, Lowenstein PR, et al. Platelets mediate cytotoxic T lymphocyte-induced liver damage. Nat Med. 2005;11:1167–9.PubMedCrossRefPubMedCentral Iannacone M, Sitia G, Isogawa M, Marchese P, Castro MG, Lowenstein PR, et al. Platelets mediate cytotoxic T lymphocyte-induced liver damage. Nat Med. 2005;11:1167–9.PubMedCrossRefPubMedCentral
Metadata
Title
Preoperative Aspartate Aminotransferase to Platelet Ratio is an Independent Prognostic Factor for Hepatitis B-Induced Hepatocellular Carcinoma After Hepatic Resection
Authors
Shun-Li Shen, MD, PhD
Shun-Jun Fu, MD
Bin Chen, MD, PhD
Ming Kuang, MD, PhD
Shao-Qiang Li, MD, PhD
Yun-Peng Hua, MD, PhD
Li-Jian Liang, MD
Pi Guo, MD
Yuantao Hao, MD, PhD
Bao-Gang Peng, MD, PhD
Publication date
01-11-2014
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue 12/2014
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-014-3771-x

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