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High risk of hepatocellular carcinoma and death in patients with immune-tolerant-phase chronic hepatitis B
Gut ( IF 23.0 ) Pub Date : 2017-10-21 , DOI: 10.1136/gutjnl-2017-314904
Gi-Ae Kim , Young-Suk Lim , Seungbong Han , Jonggi Choi , Ju Hyun Shim , Kang Mo Kim , Han Chu Lee , Yung Sang Lee

Objective High serum HBV DNA levels are associated with high risks of hepatocellular carcinoma (HCC) and cirrhosis in patients with chronic hepatitis B (CHB). Although the immune-tolerant (IT) phase is characterised by high circulating HBV DNA levels, it remains unknown whether antiviral treatment reduces risks of HCC and mortality. Design This historical cohort study included HBeAg-positive patients with CHB with high HBV DNA levels (≥20 000 IU/mL) and no evidence of cirrhosis at a tertiary referral hospital in Korea from 2000 to 2013. The clinical outcomes of 413 untreated IT-phase patients with normal alanine aminotransferase (ALT) levels (females, <19 IU/mL; males, <30 IU/mL) were compared with those of 1497 immune-active (IA)-phase patients (ALT ≥80 IU/mL) treated with nucleos(t)ide analogues. Results The IT group was significantly younger than the IA group (mean age, 38 vs 40 years at baseline, p=0.04). The 10-year estimated cumulative incidences of HCC (12.7% vs 6.1%; p=0.001) and death/transplantation (9.7% vs 3.4%; p<0.001) were significantly higher in the IT group than the IA group. In multivariable analyses, the IT group showed a significantly higher risk of HCC (HR 2.54; 95% CI 1.54 to 4.18) and death/transplantation (HR 3.38; 95% CI 1.85 to 6.16) than the IA group, which was consistently identified through inverse probability treatment weighting, propensity score-matched and competing risks analyses. Conclusions Untreated IT-phase patients with CHB had higher risks of HCC and death/transplantation than treated IA-phase patients. Unnecessary deaths could be prevented through earlier antiviral intervention in select IT-phase patients.

中文翻译:

免疫耐受期慢性乙型肝炎患者肝细胞癌和死亡的高风险

目的 高血清 HBV DNA 水平与慢性乙型肝炎 (CHB) 患者发生肝细胞癌 (HCC) 和肝硬化的高风险相关。尽管免疫耐受 (IT) 阶段的特征是高循环 HBV DNA 水平,但抗病毒治疗是否能降低 HCC 和死亡率的风险仍然未知。设计 该历史队列研究包括 2000 年至 2013 年在韩国一家三级转诊医院中具有高 HBV DNA 水平(≥20 000 IU/mL)且无肝硬化证据的 HBeAg 阳性 CHB 患者。413 名未经治疗的 IT-将丙氨酸转氨酶 (ALT) 水平正常的期患者(女性,<19 IU/mL;男性,<30 IU/mL)与 1497 名免疫活性(IA)期患者(ALT ≥80 IU/mL)进行比较用核苷(酸)类似物处理。结果 IT 组明显比 IA 组年轻(平均年龄,基线时 38 岁 vs 40 岁,p=0.04)。IT 组的 10 年 HCC 估计累积发生率(12.7% 对 6.1%;p=0.001)和死亡/移植(9.7% 对 3.4%;p<0.001)显着高于 IA 组。在多变量分析中,IT 组的 HCC(HR 2.54;95% CI 1.54 至 4.18)和死亡/移植(HR 3.38;95% CI 1.85 至 6.16)风险显着高于 IA 组,这一点一直通过逆概率处理加权、倾向得分匹配和竞争风险分析。结论 未经治疗的 IT 期 CHB 患者比治疗的 IA 期患者具有更高的 HCC 和死亡/移植风险。
更新日期:2017-10-21
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