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乙型肝炎相关肝细胞癌复发的危险因素及切除术后独立预测评分

Risk Factors and Post-Resection Independent Predictive Score for the Recurrence of Hepatitis B-Related Hepatocellular Carcinoma.

作者信息

Hung Ivan Fan-Ngai, Wong Danny Ka-Ho, Poon Ronnie Tung-Ping, Fong Daniel Yee-Tak, Chui Ada Hang-Wai, Seto Wai-Kay, Fung James Yan-Yue, Chan Albert Chi-Yan, Yuen John Chi-Hang, Tiu Randal, Choi Olivia, Lai Ching-Lung, Yuen Man-Fung

机构信息

Department of Medicine, the University of Hong Kong, Queen Mary Hospital, Hong Kong, China.

State Key Laboratory for Liver Research, the University of Hong Kong, Queen Mary Hospital, Hong Kong, China.

出版信息

PLoS One. 2016 Feb 22;11(2):e0148493. doi: 10.1371/journal.pone.0148493. eCollection 2016.

Abstract

BACKGROUND

Independent risk factors associated with hepatitis B (HBV)-related hepatocellular carcinoma (HCC) after resection remains unknown. An accurate risk score for HCC recurrence is lacking.

METHODS

We prospectively followed up 200 patients who underwent liver resection for HBV-related HCC for at least 2 years. Demographic, biochemical, tumor, virological and anti-viral treatment factors were analyzed to identify independent risk factors associated with recurrence after resection and a risk score for HCC recurrence formulated.

RESULTS

Two hundred patients (80% male) who underwent liver resection for HBV-related HCC were recruited. The median time of recurrence was 184 weeks (IQR 52-207 weeks) for the entire cohort and 100 patients (50%) developed HCC recurrence. Stepwise Cox regression analysis identified that one-month post resection HBV DNA >20,000 IU/mL (p = 0.019; relative risk (RR) 1.67; 95% confidence interval (C.I.): 1.09-2.57), the presence of lymphovascular permeation (p<0.001; RR 2.69; 95% C.I.: 1.75-4.12), microsatellite lesions (p<0.001; RR 2.86; 95% C.I.: 1.82-4.51), and AFP >100ng/mL before resection (p = 0.021; RR 1.63; 95% C.I.: 1.08-2.47) were independently associated with HCC recurrence. Antiviral treatment before resection (p = 0.024; RR 0.1; 95% C.I.: 0.01-0.74) was independently associated with reduced risk of HCC recurrence. A post-resection independent predictive score (PRIPS) was derived and validated with sensitivity of 75.3% and 60.6% and specificity of 55.7% and 79.2%, to predict the 1- and 3-year risks for the HCC recurrence respectively with the hazard ratio of 2.71 (95% C.I.: 2.12-3.48; p<0.001). The AUC for the 1- and 3-year prediction were 0.675 (95% C.I.: 0.6-0.78) and 0.746 (95% C.I.: 0.69-0.82) respectively.

CONCLUSION

Several tumor, virological and biochemical factors were associated with a higher cumulative risk of HCC recurrence after resection. PRIPS was derived for more accurate risk assessment. Regardless of the HBV DNA level, antiviral treatment should be given to patients before resection to reduce the risk of recurrence.

摘要

背景

肝切除术后与乙型肝炎(HBV)相关的肝细胞癌(HCC)的独立危险因素尚不清楚。目前缺乏用于预测HCC复发的准确风险评分。

方法

我们对200例行肝切除术治疗HBV相关HCC的患者进行了至少2年的前瞻性随访。分析了人口统计学、生化、肿瘤、病毒学和抗病毒治疗因素,以确定与肝切除术后复发相关的独立危险因素,并制定HCC复发风险评分。

结果

招募了200例行肝切除术治疗HBV相关HCC的患者(80%为男性)。整个队列的复发中位时间为184周(四分位间距52 - 207周),100例患者(50%)发生HCC复发。逐步Cox回归分析确定,术后1个月HBV DNA>20,000 IU/mL(p = 0.019;相对风险(RR)1.67;95%置信区间(C.I.):1.09 - 2.57)、存在淋巴管浸润(p<0.001;RR 2.69;95% C.I.:1.75 - 4.12)、微卫星灶(p<0.001;RR 2.86;95% C.I.:1.82 - 4.51)以及术前甲胎蛋白>100ng/mL(p = 0.021;RR 1.63;95% C.I.:1.08 - 2.47)与HCC复发独立相关。术前抗病毒治疗(p = 0.024;RR 0.1;95% C.I.:0.01 - 0.74)与降低HCC复发风险独立相关。得出了一个术后独立预测评分(PRIPS),并进行了验证,预测1年和3年HCC复发风险的敏感性分别为75.3%和60.6%,特异性分别为55.7%和79.2%,风险比为2.71(95% C.I.:2.12 - 3.48;p<0.001)。1年和3年预测的AUC分别为0.675(95% C.I.:0.6 - 0.78)和0.746(95% C.I.:0.69 - 0.82)。

结论

多种肿瘤、病毒学和生化因素与肝切除术后HCC复发的累积风险较高相关。得出PRIPS以进行更准确的风险评估。无论HBV DNA水平如何,术前均应给予患者抗病毒治疗以降低复发风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f0c/4762706/e869791dd4ff/pone.0148493.g001.jpg

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