Effect of Preoperative Serum HBeAg Status on Recurrence and Survival in Hepatocellular Carcinoma Patients after Radical Resection_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

SUN Huichuan , ZHANG Wei , QIN Lunxiu , YE Qinghai , WANG Lu , REN Ning , ZHUANG Pengyuan , ZHU Xiaodong , LU Lu , QIAN Yongbing , GUO Jiakai , XIANG Shijun , ZHANG Weide , FAN Jia , TANG Zhaoyou

Liver Cancer Insititute and Zhongshan Hospital, Fudan University, Shanghai 200032, China;

Corresponding author：

Keywords：

Hepatocellular carcinoma; Radical resection; HBeAg; Overall survival; Disease-free survival

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Objective 　To study the effect of HBeAg on recurrence and survival after radical resection of small (≤3 cm) hepatocellular carcinoma (HCC).
Methods 　Two hundreds and twenty-three HCC patients undergone radical resection from 1999 to 2000 were divided into two groups according to serum HBeAg status， HBeAg positive group (n=73) and HBeAg negative group (n=150). The patients’ factors, operative factors and tumorous facors were studied retrospectively between the two groups. And risk factors of overall survival (OS) and disease-free survival (DFS) were analyzed.
Results 　There were no significant differences in operative and tumorous factors between the two groups, but the HBeAg positive group were younger with more severe cirrhosis (P=0.004, P=0.008). The OS and DFS were significantly different between the HBeAg positive group and HBeAg negative group. The 1-, 3- and 5-year OS were 91.5%, 76.8%, 60.1% and 95.2%, 85.3%, 73.2%, respectively (P=0.053)； and the 1-, 3- and 5-year DFS were 73.3%, 53.7%, 40.3% and 86.6%, 65.5%, 54.5%, respectively (P=0.002). Multivariate analysis revealed that age ＞50 years, HBeAg positive and macronodular cirrhosis were significantly related to OS, and HBeAg positive, multiple tumor nodulars were significantly related to DFS. Positive serum HBeAg status was an independent risk factor for both OS and DFS.
Conclusion 　Positive serum HBeAg is closely related to early recurrence and survival after radical resection of patients with small HCC.

Citation： SUN Huichuan,ZHANG Wei,QIN Lunxiu,YE Qinghai,WANG Lu,REN Ning,ZHUANG Pengyuan,ZHU Xiaodong,LU Lu,QIAN Yongbing,GUO Jiakai,XIANG Shijun,ZHANG Weide,FAN Jia,TANG Zhaoyou. Effect of Preoperative Serum HBeAg Status on Recurrence and Survival in Hepatocellular Carcinoma Patients after Radical Resection. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2007, 14(1): 32-38. doi: Copy

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8.	Grazi GL, Cescon M, Ravaioli M, et al. Liver resection for he-patocellular carcinoma in cirrhotics and noncirrhotics. Evaluation of clinicopathologic features and comparison of risk factors for long-term survival and tumour recurrence in a single centre [J]. Aliment Pharmacol Ther， 2003; 17 Suppl 2∶119.
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15.	Kubo S, Hirohashi K, Tanaka H, et al. Effect of viral status on recurrence after liver resection for patients with hepatitis B virus-related hepatocellular carcinoma [J]. Cancer， 2000; 88(5)∶1016.
16.	Chen JH, Chau GY, Lui WY, et al. Surgical results in patients with hepatitis B-related hepatocellular carcinoma and positive hepatitis B early antigen [J]. World J Surg， 2000; 24(3)∶383.
17.	Sun HC, Tang ZY, Wang L, et al. Postoperative interferon alpha treatment postponed recurrence and improved overall survival in patients after curative resection of HBV-related hepatocellular carcinoma: a randomized clinical trial [J]. J Cancer Res Clin Oncol， 2006; 132(7)∶458.
18.	Jiao LR, Habib NA. Randomized clinical trial of the effects of abdominal drainage after elective hepatectomy using the crushing clamp method (Br J Surg 2006; 93∶422-426) [J]. Br J Surg， 2006; 93(8)∶1024.
19.	Couinaud C. The anatomy of the liver [J]. Ann Ital Chir, 1992; 63(6)∶693.
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22.	Capussotti L, Muratore A, Amisano M, et al. Liver resection for hepatocellular carcinoma on cirrhosis: analysis of mortality, morbidity and survival——a European single center experience [J]. Eur J Surg Oncol， 2005; 31(9)∶986.
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24.	Tung-Ping Poon R, Fan ST, Wong J. Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma [J]. Ann Surg， 2000; 232(1)∶10.
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28.	Lai CL, Lim SG, Brown NA, et al. A dose-finding study of once-daily oral telbivudine in HBeAg-positive patients with chronic hepatitis B virus infection [J]. Hepatology， 2004; 40(3)∶719.
29.	Kurihara T, Imazeki F, Yokosuka O, et al. Effect of lamivudine in HBeAg-positive chronic hepatitis B: discordant effect on HBeAg and HBV DNA according to pretreatment ALT level [J]. World J Gastroenterol， 2005; 11(22)∶3346.
30.	Fujioka S. Case-control study of lamivudine treatment in patients with HBV-related hepatocellular carcinoma [J]. Hepatology, 2003; 38(4)∶719A.
31.	Cheng SQ, Wu MC, Chen H, et al. Antiviral therapy using lamivudine and thymosin alpha(1) for hepatocellular carcinoma coexisting with chronic hepatitis B infection [J]. Hepato Gastroenterol, 2006; 53(68)∶249.

1. 　Tang ZY, Yu YQ, Zhou XD, et al. Progress and prospects in hepatocellular carcinoma surgery [J]. Ann Chir， 1998; 52(6)∶558.
2. 　Tang ZY, Ye SL, Liu YK, et al. A decade’s studies on metastasis of hepatocellular carcinoma [J]. J Cancer Res Clin Oncol， 2004; 130(4)∶187.
3. 　Poon RT, Ng IO, Lau C, et al. Correlation of serum basic fibroblast growth factor levels with clinicopathologic features and postoperative recurrence in hepatocellular carcinoma [J]. Am J Surg， 2001; 182(3)∶298.
4. 　Dusheiko G. Candidates for therapy: HBV [J]. J Hepatol， 2006; 44(1 Suppl)∶S84.
5. 　Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level [J]. JAMA， 2006; 295(1)∶65.
6. 　Colombo M, Donato MF. Prevention of hepatocellular carcinoma [J]. Semin Liver Dis， 2005; 25(2)∶155.
7. 　Hanazaki K, Kajikawa S, Shimozawa N, et al. Survival and recurrence after hepatic resection of 386 consecutive patients with hepatocellular carcinoma [J]. J Am Coll Surg， 2000; 191(4)∶381.
8. 　Grazi GL, Cescon M, Ravaioli M, et al. Liver resection for he-patocellular carcinoma in cirrhotics and noncirrhotics. Evaluation of clinicopathologic features and comparison of risk factors for long-term survival and tumour recurrence in a single centre [J]. Aliment Pharmacol Ther， 2003; 17 Suppl 2∶119.
9. 　Peng SY, Chen WJ, Lai PL, et al. High alpha-fetoprotein level correlates with high stage, early recurrence and poor prognosis of hepatocellular carcinoma: significance of hepatitis virus infection, age, p53 and beta-catenin mutations [J]. Int J Cancer， 2004; 112(1)∶44.
10. 　Hanazaki K, Matsushita A, Nakagawa K, et al. Risk factors of intrahepatic recurrence after curative resection of hepatocellular carcinoma [J]. Hepatogastroenterology， 2005; 52(62)∶580.
11. 　Adachi E, Maehara S, Tsujita E, et al. Clinicopathologic risk factors for recurrence after a curative hepatic resection for hepatocellular carcinoma [J]. Surgery， 2002; 131(1 Suppl)∶S148.
12. 　Poon RT, Fan ST, Ng IO, et al. Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma [J]. Cancer， 2000; 89(3)∶500.
13. 　Yang HI, Lu SN, Liaw YF, et al. Hepatitis B e antigen and the risk of hepatocellular carcinoma [J]. N Engl J Med， 2002; 347(3)∶168.
14. 　Kubo S, Hirohashi K, Yamazaki O, et al. Effect of the presence of hepatitis B e antigen on prognosis after liver resection for hepatocellular carcinoma in patients with chronic hepatitis B [J]. World J Surg， 2002; 26(5)∶555.
15. 　Kubo S, Hirohashi K, Tanaka H, et al. Effect of viral status on recurrence after liver resection for patients with hepatitis B virus-related hepatocellular carcinoma [J]. Cancer， 2000; 88(5)∶1016.
16. 　Chen JH, Chau GY, Lui WY, et al. Surgical results in patients with hepatitis B-related hepatocellular carcinoma and positive hepatitis B early antigen [J]. World J Surg， 2000; 24(3)∶383.
17. 　Sun HC, Tang ZY, Wang L, et al. Postoperative interferon alpha treatment postponed recurrence and improved overall survival in patients after curative resection of HBV-related hepatocellular carcinoma: a randomized clinical trial [J]. J Cancer Res Clin Oncol， 2006; 132(7)∶458.
18. 　Jiao LR, Habib NA. Randomized clinical trial of the effects of abdominal drainage after elective hepatectomy using the crushing clamp method (Br J Surg 2006; 93∶422-426) [J]. Br J Surg， 2006; 93(8)∶1024.
19. 　Couinaud C. The anatomy of the liver [J]. Ann Ital Chir, 1992; 63(6)∶693.
20. 　Edmondson HA， Steiner PE. Primary carcinoma of the liver: a study of 100 cases among 48 900 necropsies [J]. Cancer, 1954; 7(3)∶462.
21. 　Ohata K, Hamasaki K, Toriyama K, et al. High viral load is a risk factor for hepatocellular carcinoma in patients with chronic hepatitis B virus infection [J]. J Gastroenterol Hepatol， 2004; 19(6)∶670.
22. 　Capussotti L, Muratore A, Amisano M, et al. Liver resection for hepatocellular carcinoma on cirrhosis: analysis of mortality, morbidity and survival——a European single center experience [J]. Eur J Surg Oncol， 2005; 31(9)∶986.
23. 　Hanazaki K, Matsushita A, Nakagawa K, et al. Risk factors of long-term survival and recurrence after curative resection of hepatocellular carcinoma [J]. Hepatogastroenterology， 2005; 52(62)∶552.
24. 　Tung-Ping Poon R, Fan ST, Wong J. Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma [J]. Ann Surg， 2000; 232(1)∶10.
25. 　Hanazaki K, Kajikawa S, Shimozawa N, et al. Perioperative blood transfusion and survival following curative hepatic resection for hepatocellular carcinoma [J]. Hepatogastroenterology， 2005; 52(62)∶524.
26. 　Nakanishi S, Michitaka K, Miyake T, et al. Decompensated hepatitis B virus-related cirrhosis successfully treated with lamivudine allowing surgery for hepatocellular carcinoma [J]. Intern Med， 2003; 42(5)∶416.
27. 　Nagamatsu H, Itano S, Nagaoka S, et al. Prophylactic lamivudine administration prevents exacerbation of liver damage in HBe antigen positive patients with hepatocellular carcinoma undergoing transhepatic arterial infusion chemotherapy [J]. Am J Gastroenterol， 2004; 99(12)∶2369.
28. 　Lai CL, Lim SG, Brown NA, et al. A dose-finding study of once-daily oral telbivudine in HBeAg-positive patients with chronic hepatitis B virus infection [J]. Hepatology， 2004; 40(3)∶719.
29. 　Kurihara T, Imazeki F, Yokosuka O, et al. Effect of lamivudine in HBeAg-positive chronic hepatitis B: discordant effect on HBeAg and HBV DNA according to pretreatment ALT level [J]. World J Gastroenterol， 2005; 11(22)∶3346.
30. 　Fujioka S. Case-control study of lamivudine treatment in patients with HBV-related hepatocellular carcinoma [J]. Hepatology, 2003; 38(4)∶719A.
31. 　Cheng SQ, Wu MC, Chen H, et al. Antiviral therapy using lamivudine and thymosin alpha(1) for hepatocellular carcinoma coexisting with chronic hepatitis B infection [J]. Hepato Gastroenterol, 2006; 53(68)∶249.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of Preoperative Serum HBeAg Status on Recurrence and Survival in Hepatocellular Carcinoma Patients after Radical Resection

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