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经核苷(酸)类似物治疗实现病毒血症持续消失的慢性乙型肝炎患者肝细胞癌发生的累积发病率及危险因素

Cumulative incidence and risk factors for the development of hepatocellular carcinoma in patients with chronic hepatitis B who achieved sustained disappearance of viremia by nucleos(t)ide analog treatment.

作者信息

Ando Yusuke, Ishigami Masatoshi, Ishizu Yoji, Kuzuya Teiji, Honda Takashi, Hayashi Kazuhiko, Ishikawa Tetsuya, Nakano Isao, Hirooka Yoshiki, Goto Hidemi

机构信息

Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

出版信息

Hepatol Res. 2018 Feb;48(3):E240-E251. doi: 10.1111/hepr.12976. Epub 2017 Sep 30.

DOI:10.1111/hepr.12976
PMID:28865403
Abstract

AIM

Nucleos(t)ide analog (NA) therapy has been reported to reduce the risk of hepatocellular carcinoma (HCC). However, some patients who achieve hepatitis B virus (HBV)-DNA disappearance from serum by NA develop HCC. In this study, we investigated the cumulative incidence and risk factors for HCC in patients with chronic hepatitis B (CHB) who achieved sustained disappearance of viremia by NA treatment.

METHODS

A total of 133 CHB patients (median age, 51 years; 79 men [59%]; 28 with cirrhosis [21%]) who received NA therapy and achieved HBV-DNA disappearance from serum were analyzed retrospectively. We evaluated the cumulative incidence of HCC and risk factors associated with HCC based on data collected at the time of HBV-DNA disappearance.

RESULTS

Thirteen patients developed HCC during the follow-up period. The 1-, 3-, and 5-year cumulative incidence of HCC was 0.0%, 7.8%, and 11.1%, respectively. In multivariate analysis, advanced age (hazard ratio [HR], 4.601; 95% confidence interval [CI], 1.220-17.351; P = 0.024), liver cirrhosis (HR, 5.563; 95% CI, 1.438-21.519; P = 0.013), and higher HBV core-related antigen (HBcrAg) levels (HR, 13.532; 95% CI, 1.683-108.815; P = 0.014) at the time of HBV-DNA disappearance were significantly associated with the development of HCC.

CONCLUSION

Our findings indicate the importance of continuous HCC surveillance especially in patients with advanced age, cirrhosis, and/or higher serum levels of HBcrAg, even if they achieve HBV-DNA disappearance.

摘要

目的

核苷(酸)类似物(NA)治疗已被报道可降低肝细胞癌(HCC)的风险。然而,一些通过NA治疗使血清中乙型肝炎病毒(HBV)-DNA消失的患者仍会发生HCC。在本研究中,我们调查了通过NA治疗实现病毒血症持续消失的慢性乙型肝炎(CHB)患者中HCC的累积发病率及危险因素。

方法

对133例接受NA治疗且血清HBV-DNA消失的CHB患者(中位年龄51岁;79例男性[59%];28例肝硬化患者[21%])进行回顾性分析。我们根据HBV-DNA消失时收集的数据评估了HCC的累积发病率及与HCC相关的危险因素。

结果

13例患者在随访期间发生了HCC。HCC的1年、3年和5年累积发病率分别为0.0%、7.8%和11.1%。多因素分析显示,HBV-DNA消失时高龄(风险比[HR],4.601;95%置信区间[CI],1.220 - 17.351;P = 0.024)、肝硬化(HR,5.563;95% CI,1.438 - 21.519;P = 0.013)以及较高的HBV核心相关抗原(HBcrAg)水平(HR,13.532;95% CI,1.683 - 108.815;P = 0.014)与HCC的发生显著相关。

结论

我们的研究结果表明,即使患者实现了HBV-DNA消失,持续进行HCC监测也很重要,尤其是对于高龄、肝硬化和/或血清HBcrAg水平较高的患者。

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