Pretreatment glucose status determines HCC development in HCV patients with mild liver disease after curative antiviral therapy.
Pretreatment glucose status determines HCC development in HCV patients with mild liver disease after curative antiviral therapy.
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DOI：
10.1097/md.0000000000004157
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发表时间：
2016-07
期刊：
影响因子：
1.6
通讯作者：
Yu ML
中科院分区：
文献类型：
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作者：
Huang CF;Yeh ML;Huang CY;Tsai PC;Ko YM;Chen KY;Lin ZY;Chen SC;Dai CY;Chuang WL;Huang JF;Yu ML
虽然已知糖尿病（DM）会增加丙型肝炎病毒（HCV）相关肝细胞癌（HCC）的风险，但在接受抗病毒治疗的慢性丙型肝炎（CHC）患者中，动态葡萄糖状态对HCC发生的影响尚不清楚。总共有1112名活检证实的患者接受了聚乙二醇干扰素/利巴韦林治疗。通过75 g口服葡萄糖耐量试验（OGTT）测定治疗前和治疗后的葡萄糖状态，以评估葡萄糖状态与HCC发展之间的关系。在接受评估的1112例患者中，93例（8.4%）在5183.8人年随访期间发生HCC（年发病率：1.79%）。糖尿病仅影响轻度肝病（F0-2）和持续病毒学反应（SVR）患者发生CC的风险，而对其他患者亚群没有影响。cox回归分析显示，轻度肝病患者发生HCC及SVR相关性最强的因素是DM（风险比[HR]/ 95%可信区间[CI]: 3.79/1.42 ~ 10.136, P = 0.008），其次是年龄（HR/CI: 1.06/1.001 ~ 1.117, P = 0.046）和血小板计数（HR/CI: 0.989/0.979 ~ 1.000, P = 0.05）。治疗前伴有正常血糖、糖尿病前期、亚糖尿病（sdm前期）和糖尿病的SVR患者比例分别为45.3% （n = 267）、29.9% （n = 176）、15.6% （n = 92）和9.2% （n = 54）。血糖正常、sdm前期、DM患者HCC发生率分别为1.1%、3.7%、11.1%（趋势P < 0.001）。19例HCC患者中有16例（84.2%）在抗病毒治疗前存在血糖异常（包括6例糖尿病和10例前sdm）。与血糖正常的患者相比，HCC的发生率从sdm前（HR: 3.6, P = 0.05）到DM （HR: 11.6, P = 0.001）逐渐升高（调整趋势P = 0.004）。我们得出结论，糖尿病是SVR合并轻度肝病患者发生HCC的关键决定因素。sdm前的状态增加了HCC的风险，这些患者在病毒根除后也应该仔细监测HCC。
Supplemental Digital Content is available in the text Although diabetes mellitus (DM) is known to increase the risk of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC), the impact of dynamic glucose status on HCC occurrence in chronic hepatitis C (CHC) patients receiving antiviral therapy is unclear. In total, 1112 biopsy-proven patients treated with peginterferon/ribavirin were enrolled in this study. Both pretreatment and post-treatment glucose status, including 75 g oral glucose tolerance test (OGTT), were measured to evaluate the association between glucose status and the development of HCC. Of the 1112 patients evaluated, 93 (8.4%) developed HCC >5183.8 person-years of follow-up (annual incidence rate: 1.79%). DM only influenced the risk of developing CC in patients with mild liver disease (F0-2) and a sustained virological response (SVR) but not in other patient subpopulations. Cox-regression analysis demonstrated that the strongest factor associated with HCC in patients with mild liver disease and SVR was the presence of DM (hazard ratio [HR]/95 % confidence intervals [CI]: 3.79/1.420–10.136, P = 0.008), followed by age (HR/CI: 1.06/1.001–1.117, P = 0.046) and platelet count (HR/CI: 0.989/0.979–1.000, P = 0.05). The percentages of SVR patients with F0-2 with normoglycemia, pre-DM, sub-DM (pre-sDM), and DM before treatment were 45.3% (n = 267), 29.9% (n = 176), 15.6% (n = 92), and 9.2% (n = 54), respectively. The percentages of HCC in patients with normoglycemia, pre-sDM, and DM were 1.1%, 3.7%, and 11.1%, respectively (trend P < 0.001). Sixteen of the 19 (84.2 %) HCC patients possessed glucose abnormality (including 6 patients with DM and 10 patients with pre-sDM) before antiviral therapy. Compared to patients with normoglycemia, the incidence of HCC increased gradually from pre-sDM (HR: 3.6, P = 0.05) to DM (HR: 11.6, P = 0.001) (adjusted trend P = 0.004). We concluded that DM is a critical determinant for the development of HCC in SVR patients with mild liver disease. Pre-sDM status carried an additional risk for HCC, and these patients should also be carefully monitored for HCC after viral eradication.