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代谢危险因素对慢性乙型肝炎患者肝细胞癌和肝相关死亡风 [复制链接]

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发表于 2017-7-18 15:39 |只看该作者 |倒序浏览 |打印

    Gastroenterology. 2017 Jul 12. pii: S0016-5085(17)35866-3. doi: 10.1053/j.gastro.2017.07.001. [Epub ahead of print]
    Influence of Metabolic Risk Factors on Risk of Hepatocellular Carcinoma and Liver-related Death in Men with Chronic Hepatitis B: A Large Cohort Study.Yu MW1, Lin CL2, Liu CJ3, Yang SH4, Tseng YL4, Wu CF4.
    Author information
    1Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. Electronic address: [email protected].2Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Taipei, Taiwan.3Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.4Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.

    AbstractBACKGROUND & AIMS: Little is known about the absolute risk of hepatocellular carcinoma (HCC) and liver-disease related death, in association with metabolic risk factors, for patients with hepatitis B virus (HBV) infection.
    METHODS: We collected data from 5373 male Taiwanese civil servants who visited Taiwan's Government Employees' Central Clinics and received routine free physical examinations from 1989 through 1992. We obtained information on liver-related morbidity and mortality in HBV carriers, 40-65 years old (n=1690), with different metabolic risk factors. We compared their medical histories with those of study participants without HBV or HCV infection in the same age range (n=1289). We used patients' baseline data on obesity, diabetes, hypertriglyceridemia, and high blood pressure to assign them to metabolic risk categories. We then performed a case-cohort analysis of the effects of hepatitis B viral factors on risk for HCC, based on metabolic factors and insulin resistance.
    RESULTS: Over median follow-up period of 19 years, 158 of the 1690 HBV carriers developed HCC and 126 died from liver-related diseases. Among participants without HBV or HCV infection, only 6 developed HCC or died from liver-related disease. HBV carriers with different metabolic risk factors had significant differences in cumulative incidence of HCC and liver-related death. Patients with 3 or more metabolic risk factors had a substantially higher risk for HCC (10-year cumulative incidence, 13.60%) than patients with a low metabolic risk profile (10-year cumulative incidence, 4.83%; adjusted-hazard ratio [aHR], 2.32; 95% CI, 1.18-4.54). Smoking had a significant effect on this association (Pinteraction = .0044). Having 3 or more metabolic risk factors, compared with no factors, significantly increased the risk of HCC (aHR, 5.06; 95% CI, 2.23-11.47) and 10-year cumulative incidence of HCC (25.0% in smokers with 3 or more metabolic risk factors vs 3.87% in smokers with none; P< .0001) in smokers, but did not increase risk of HCC in nonsmokers. Metabolic risk factors and insulin resistance had the largest effect on HCC risk in patients with levels of HBV-DNA <10000 copies/mL.
    CONCLUSIONS: In a study of men with chronic HBV infection ages 40-65 years in Taiwan, we associated a high burden of metabolic risk factors with increased risk of HCC; smoking has a significant effect on this association.

    Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.



    KEYWORDS: ALT; Fatty liver; GGT; liver cancer

    PMID:28711626DOI:10.1053/j.gastro.2017.07.001



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发表于 2017-7-18 15:40 |只看该作者
消化内科。 2017年7月12日。pii:S0016-5085(17)35866-3。 doi:10.1053 / j.gastro.2017.07.001。 [提前印刷]
代谢危险因素对慢性乙型肝炎患者肝细胞癌和肝相关死亡风险的影响:大队列研究。
Yu MW1,Lin CL2,Liu CJ3,Yang SH4,Tseng YL4,Wu CF4。
作者信息

1
    台湾台北大学公共卫生学院流行病与预防医学研究所。电子地址:[email protected]
2
    台北市台北市医院仁爱分院胃肠病科。
3
    台湾大学医院消化内科,台湾大学附属医院和台湾大学医学院临床医学研究生院台湾台北。
4
    台湾台北大学公共卫生学院流行病与预防医学研究所。

抽象
背景与目的:

对于乙型肝炎病毒(HBV)感染患者,与代谢危险因素相关的肝细胞癌(HCC)和肝病相关死亡的绝对风险知之甚少。
方法:

收集了来自台湾政府雇员中心诊所的5373名台湾公务员资料,从1989年至1992年间接受了常规免费体检。我们获得40-65岁乙肝携带者肝脏相关发病率和死亡率信息(n = 1690),具有不同的代谢危险因素。我们将他们的病史与没有HBV或HCV感染的研究参与者的年龄进行比较(n = 1289)。我们使用患者的肥胖,糖尿病,高甘油三酯血症和高血压的基准数据将其分配给代谢风险类别。然后,我们根据代谢因素和胰岛素抵抗,对乙型肝炎病毒因子对HCC风险的影响进行了病例分析。
结果:

中位随访时间为19年,1690例HBV携带者中有158例发生HCC,126例死于肝脏相关疾病。在没有HBV或HCV感染的参与者中,只有6例发生HCC或死于肝脏相关疾病。具有不同代谢危险因素的HBV携带者在肝癌和肝脏相关死亡的累积发病率方面有显着差异。具有3个或更多代谢危险因素的患者HCC(10年累积发生率为13.60%)的风险明显高于代谢风险较低的患者(10年累积发生率为4.83%;调整风险比[aHR] ,2.32; 95%CI,1.18-4.54)。吸烟对这种关联有显着影响(Pinteraction = .0044)。 3个或更多的代谢危险因素与无因素相比,显着增加了HCC的风险(aHR,5.06; 95%CI,2.23-11.47)和HCC的10年累积发病率(25.0%的吸烟者具有3种或更多的代谢吸烟者的吸烟者的危险因素与吸烟者的比例为3.87%,P <0.0001),但不增加吸烟者HCC的风险。代谢危险因素和胰岛素抵抗对HBV-DNA水平高于10000拷贝/ mL的患者HCC风险影响最大。
结论:

在台湾一名40-65岁的慢性HBV感染男性研究中,我们将代谢危险因素与HCC风险增加相关联;吸烟对这种关联有重大影响。

版权所有©2017 AGA Institute。由Elsevier Inc.发布。保留所有权利。
关键词:

ALT;脂肪肝; GGT;肝癌

结论:
    28711626
DOI:
    10.1053 / j.gastro.2017.07.001

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发表于 2017-7-18 15:42 |只看该作者
HCC risk increases in men with HBV, multiple metabolic risk factors

Yu MW, et al. Gastroenterol. 2017;doi:10.1053/j.gastro.2017.07.001.
July 17, 2017

Men aged 40 to 65 years with chronic hepatitis B and a high burden of metabolic risk factors had increased risk for hepatocellular carcinoma, especially is they were smokers, according to a recently published study.

“If our findings are confirmed, then the results of this study suggest that a substantial fraction of HBV-related HCC cases, especially those with low viral loads, might be prevented by management of metabolic risk factors and cessation of smoking,” Ming-Whei Yu, PhD, from the National Taiwan University, and colleagues wrote.

The study comprised 1,690 men who were HBsAg-positive and a control cohort of 1,289 men negative for both HBsAg and hepatitis C. In the HBsAg-positive cohort, median age was 48.4 years (range, 43.8-56.8 years), median BMI was 23.7 kg/m2 (range, 22.1-25.4 kg/m2) and 31.6% were obese. The researchers reported that the control cohort had similar characteristics.

Compared with controls, patients with HBV had lower prevalence of impaired fasting glucose, hypertriglyceridemia, hypercholesterolemia and high blood pressure, even after adjusting for age and alanine aminotransferase levels (P < .05), and a higher proportion of history of chronic liver disease and prevalence of elevated liver enzymes (P < .0001).

In the HBV cohort, 158 developed HCC during follow-up. Overall, 305 patients died; 126 died of liver-related disease, of which HCC caused 94 deaths. The cumulative incidence of HCC (P = .0468) and liver-related death (P = .0068) increased as metabolic risk-factor sum increased.

Results of a 10-year cumulative analysis showed that HCC incidence increased from 4.83% among patients with an optimal risk-factor profile to 13.6% among those with three or more metabolic risk factors, of whom 92.5% were obese and 45.3% had diabetes. After adjusting for age, smoking status, alcohol consumption and family history of HCC, patients with three or more metabolic risk factors still had a significantly higher risk for HCC (HR = 2.32; 95% CI, 1.18-4.54).

In the control cohort, by comparison, there were five cases of HCC during follow-up and 135 deaths, of which three followed HCC development and one followed cirrhosis development. The risk for liver-related events also increased in control participants who had three or more metabolic risk factors (HR = 8.57; 95% CI, 1.18-62.15).

The researchers observed a significant increase in risk for HCC among smokers with three or more metabolic risk factors (HR = 5.06; 95% CI, 2.23-11.47), compared with both smokers with fewer metabolic risk factors and nonsmokers with any number of metabolic risk factors. However, the risk for HCC among those with three or more metabolic risk factors tended to decrease after 5 years of smoking cessation.

“This study demonstrated that metabolic risk factor burden was a significant independent predictor of HBV-related HCC, even after accounting for major viral factors and other recognized risk factors,” the researchers concluded. “Thus, despite the majority of HBV-related HCC cases accounted for by high viral load, our data suggest that there exists some cases of HBV-related HCC arising in the background of metabolic syndrome, which represents a distinct clinicopathological entity that has not yet achieved adequate attention in clinical practice and disease prevention.” – by Talitha Bennett

Disclosure: The researchers report no relevant financial disclosures.

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发表于 2017-7-18 15:42 |只看该作者
男性肝细胞肝癌风险增加,多种代谢危险因素

Yu MW,et al。 Gastroenterol。 2017; DOI:10.1053 / j.gastro.2017.07.001。
2017年7月17日

根据最近公布的一项研究,40至65岁的慢性乙型肝炎患者和代谢危险因素的高负担增加了肝细胞癌的风险,特别是吸烟者。

“如果我们的研究结果得到证实,那么这项研究的结果表明,通过管理代谢危险因素和停止吸烟可以预防HBV相关HCC病例,特别是病毒载量低的病例的很大一部分,”Ming-Whei台湾大学的俞博士和同事写道。

HBsAg阳性组HBsAg阳性组为1,690例HBsAg阳性对照组,男性为1,289例,HBsAg阳性组为48.4岁(中位年龄43.8-56.8岁),平均BMI为23.7 kg / m2(范围22.1-25.4 kg / m2),肥胖31.6%。研究人员报告说,对照组具有相似的特征。

与对照组相比,即使在调整年龄和丙氨酸氨基转移酶水平(P <0.05)之后,HBV患者的空腹血糖,高甘油三酯血症,高胆固醇血症和高血压患病率较低,慢性肝病史比例较高,肝酶升高(P <0.0001)。

在HBV队列中,158例随访期间发展为HCC。总共305例患者死亡; 126例死于肝脏相关疾病,其中HCC引起94例死亡。随着代谢风险因子和的增加,HCC(P = 0.0468)和肝相关死亡(P = .0068)的累积发生率增加。

10年累积分析结果显示,3例以上代谢危险因素患者,HCC发生率从4​​.83%升至13.6%,其中92.5%为肥胖者,45.3%为糖尿病患者。调整年龄,吸烟状况,酒精消费量和肝癌家族史后,有三种或更多代谢危险因素的患者HCC风险显着升高(HR = 2.32; 95%CI,1.18-4.54)。

对照组比较,随访期间共发生肝癌5例,死亡135例,其中肝癌发生3例,肝硬化发生1例。具有三种或更多代谢危险因素的对照参与者肝脏相关事件风险也有所增加(HR = 8.57; 95%CI,1.18-62.15)。

研究人员观察到,与具有较少代谢危险因素的吸烟者相比,具有三种或更多代谢危险因素(HR = 5.06; 95%CI,2.23-11.47)的吸烟者的HCC风险显着增加,并且具有任何代谢风险的非吸烟者因素。然而,三年以上代谢危险因素患者HCC风险在戒烟5年后有下降趋势。

研究人员总结说:“这项研究表明,代谢危险因子负荷是HBV相关HCC的重要独立预测因子,即使在考虑了主要病毒因子和其他认可风险因素后也是如此。 “因此,尽管大部分与HBV相关的HCC病例占高病毒载量,但我们的数据表明,在代谢综合征背景下存在一些与HBV相关的HCC病例,这些病例代表了尚未形成的独特临床病理学实体在临床实践和疾病预防方面得到了充分的关注。“ - 由Talitha Bennett

披露:研究人员报告没有相关的财务披露。
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