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Original Investigation |

Prediction of Hepatocellular Carcinoma Recurrence in Patients With Low Hepatitis B Virus DNA Levels and High Preoperative Hepatitis B Surface Antigen Levels

Gang Huang, MD1; Wan Yee Lau, MD, FRCS1,2; Wei-ping Zhou, MD, PhD1; Feng Shen, MD, PhD1; Ze-ya Pan, MD1; Sheng-xian Yuan, MD1; Meng-chao Wu, MD1
[+] Author Affiliations
1Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
2Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region
JAMA Surg. 2014;149(6):519-527. doi:10.1001/jamasurg.2013.4648.
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Importance  In patients with low viral loads, high levels of hepatitis B surface antigen (HBsAg) have been shown to predict development of hepatocellular carcinoma (HCC). Whether high levels of HBsAg increase the risk for HCC recurrence after hepatic resection remains unknown.

Objective  To investigate the association between levels of HBsAg and the risk for tumor recurrence after curative resection in HCC patients with low levels of hepatitis B virus (HBV) DNA.

Design, Setting, and Participants  We performed a retrospective analysis of the clinical data of 1062 patients with low HBV DNA levels (<200 IU/mL) who underwent partial hepatectomy for HCC. In particular, we investigated the association between levels of HBsAg and recurrence of HCC.

Exposure  Partial hepatectomy for HCC.

Main Outcomes and Measures  The risk for first tumor recurrence between patients with high and low HBsAg levels. We calculated cumulative incidences and hazard ratios after adjusting for competing mortality.

Results  The risk for tumor recurrence increased with HBsAg levels of 1000 IU/mL or greater. When we compared the groups with low (<1000 IU/mL) and high (≥1000 IU/mL) HBsAg levels, the 5-year disease-free survival rate (46.1% vs 34.1% [P = .002]) and the overall survival rate (57.5% vs 48.8% [P = .004]) were better in the group with low HBsAg levels. On multivariate analysis, hepatitis B e antigen seropositivity, HBsAg level of 1000 IU/mL or greater, tumor size of greater than 5 cm, blood transfusion, surgical margin of less than 1.0 cm, the presence of satellite nodules, and the presence of portal vein tumor thrombus were independent risk factors for HCC recurrence. When compared with hepatitis B e antigen status, HBsAg level better predicted recurrence of HCC.

Conclusions and Relevance  A preoperative HBsAg level of 1000 IU/mL or greater is an independent risk factor for HCC recurrence in patients with low HBV DNA levels.

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Figure 1.
Comparison of Disease-Free Survival Among 3 Subgroups

Patients are divided into groups by level of hepatitis B surface antigen as follows: less than 100 IU/mL (group 1 [n = 280]), 100 to 999 IU/mL (group 2 [n = 342]), and 1000 IU/mL or greater (group 3 [n = 440]). For comparison of survival curves, P = .006, log-rank test.

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Figure 2.
Comparison of Disease-Free Survival Between 2 Subgroups

Patient groups are classified as having low (<1000 IU/mL [n = 622]) and high (≥1000 IU/mL [n = 440]) hepatitis B surface antigen (HBsAg) levels. P = .002, log-rank test.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.
Comparison of Overall Survival Between 2 Subgroups

Patient groups are classified as having low (<1000 IU/mL [n = 622]) and high (≥1000 IU/mL [n = 440]) hepatitis B surface antigen (HBsAg) levels. P = .004, log-rank test.

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