肝脂肪变性，年龄，HBeAg与HBV持续ALT水平相关

StephenW

Hepatic steatosis, age, HBeAg linked to persistent ALT levels in HBV

Jacobson IM, et al. Clin Gastroenterol Hepatol. 2017;doi:10.1016/j.cgh.2017.01.032.
June 26, 2017

Researchers associated hepatic steatosis, HBeAg seropositivity and age younger than 40 years with persistent increased levels of alanine aminotransferase in patients with chronic hepatitis B receiving suppressive antiviral treatment, according to data from a recently published study.

“Hepatic steatosis (nonalcoholic fatty liver disease) is common in the general population and in patients with [chronic HBV] and frequently is associated with an increase of serum transaminase levels. Consequently, the observed associations between persistent ALT level increase with steatosis and features of the metabolic syndrome despite effective antiviral therapy are not entirely surprising,” Ira M. Jacobson, MD, co-Chief Medical Editor of HCV Next, and colleagues wrote. “Our findings that younger age and HBeAg seropositivity are associated independently with failure to normalize ALT on therapy are novel and may relate to the intensity of the immune response.”
Ira Jacobson, MD

Ira Jacobson

The researchers conducted two randomized studies, one with patients who were HBeAg-negative and the other with patients who were HBeAg-positive. A total of 471 patients remained in the study to year 5, 87 of whom had persistent ALT level increase at year 5. Patients received either Viread (tenofovir disoproxil fumarate, Gilead) or Hepsera (adefovir dipivoxil, Gilead).

Compared with patients with a normal ALT level at baseline, patients with persistent ALT level increase were more likely to be younger than 40 years (41.9% vs. 57.5%; P = .012), have a BMI of 25 kg/m2 or higher (46.3% vs. 63.2%; P = .006), diabetes (2.6% vs. 8.1%; P = .023), HBeAg-positivity (33.6% vs. 52.9%; P = .001), mean HBV DNA level (1.5% vs. 1.6%; P = .018), mean HBsAg level (0.7% vs. 0.8%; P = .005) and a steatosis score of 5% or higher (22.6% or 48.8%; P < .001) and of 34% or higher (1.1% vs. 14%; P < .001).

While self-reported hyperlipidemia and hypertension did not differ between the two groups, the number of metabolic risk factors was associated with the prevalence of persistent ALT level increase. There were 28 of 212 patients with zero risk factors, 38 of 186 patients with one risk factor, 17 of 59 patients with two risk factors, and 4 of 12 patients with three or more risk factors (P = .0123).

At 5 years, characteristics of patients with persistent ALT level increase compared with those who achieved normalization showed significant association for HBV DNA levels below 69 IU/mL (P < .001), fewer patients with cirrhosis regression (P < .007), more patients with a steatosis score of 5% or higher (P < .001) and more patients with a steatosis score of 34% or higher (P < .001).

On multivariate analysis, the characteristics associated with persistent ALT level increase at year 5 remained similar to previous analyses: HBeAg seropositivity at baseline (OR = 3.297; 95% CI, 1.653-6.576), steatosis score of 5% or higher at baseline (OR = 2.236; 95% CI, 1.031-4.852) and year 5 (OR = 3.392; 95% CI, 1.56-7.375), and age 40 years or younger (OR = 2.099; 95% CI, 1.014-4.342).

“In this analysis, we have shown that despite achievement of virologic suppression in nearly all patients and demonstration of fibrosis regression in the majority of those treated with [Viread] for 5 years, approximately 1 in 5 patients fail to achieve ALT normalization,” the researchers concluded. “Both host and viral factors, particularly hepatic steatosis and HBeAg seropositivity, are important contributors to this phenomenon.” – by Talitha Bennett

Disclosure: Jacobson is a consultant for and has received honoraria and received research support from AbbVie, Bristol-Myers Squibb, Gilead, Janssen and Merck; and is a consultant for Achillion, Alnylam and Enanta.

StephenW

肝脂肪变性，年龄，HBeAg与HBV持续ALT水平相关

Jacobson IM，et al。胃肠激素肝素2017; DOI：10.1016 / j.cgh.2017.01.032。
2017年6月26日

研究人员根据最近发表的研究数据，结合肝脏脂肪变性，HBeAg血清阳性和年龄小于40岁，慢性乙型肝炎患者接受抑制性抗病毒治疗的丙氨酸氨基转移酶水平持续增加。
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“肝脂肪变性（非酒精性脂肪性肝病）在普通人群和[慢性HBV]患者中很常见，并且经常与血清转氨酶水平升高相关。因此，尽管有效的抗病毒治疗，仍然观察到持续ALT水平与脂肪变性之间的关系和代谢综合征的特征并不完全令人惊讶，“HCV Next共同首席医学编辑Ira M. Jacobson，MD和同事们写道。 “我们的研究结果显示，年龄较小的HBeAg血清阳性与治疗ALT无法正常化相关，是新的，可能与免疫反应的强度有关。”
Ira Jacobson，MD

伊拉·雅各布森

研究人员进行了两项随机研究，其中一例为HBeAg阴性患者，另一组为HBeAg阳性患者。共有471例患者在研究中仍然持续至第5年，其中87例在第5年持续ALT水平升高。患者接受了Viread（替诺福韦富地酸替莫西汀，吉利德）或Hepsera（阿德福韦酯，吉利德）。

与基线ALT水平正常的患者相比，持续ALT水平升高的患者更可能年龄小于40岁（41.9％vs. 57.5％; P = 0.012），BMI为25 kg / m2或更高（46.3％vs. 63.2％; P = .006），糖尿病（2.6％vs 8.1％; P = 0.023），HBeAg阳性（33.6％vs 52.9％; P = 0.001），平均HBV DNA水平（1.5％vs 1.6％; P = 0.018），平均HBsAg水平（0.7％vs. 0.8％; P = .005），脂肪变性评分5％或更高（22.6％或48.8％; P <0.001 ）和34％以上（1.1％对比14％; P <0.001）。

虽然自我报告的高脂血症和高血压在两组间没有差异，但代谢危险因素的数量与持续性ALT水平升高的患病率相关。 212例无危险因素的患者中有28例，186例1例危险因素中有38例，有两例危险因素的59例中有17例，有3例或以上危险因素的患者中有4例（P = 0.023）。

5年时，持续ALT水平升高的患者与实现正常化的患者相比，HBV DNA水平显着低于69 IU / mL（P <0.001），肝硬化患者减少（P <.007），更多脂肪变性评分为5％以上的患者（P <0.001），更多的脂肪变性评分为34％以上（P <0.001）。

在多变量分析中，与第二年持续ALT水平升高相关的特征与以前的分析相似：HBeAg基线血清阳性（OR = 3.297; 95％CI，1.653-6.576），基线时脂肪变性评分为5％或更高= 2.236; 95％CI，1.031-4.852）和第5年（OR = 3.392; 95％CI，1.56-7.375），40岁以下（OR = 2.099; 95％CI，1.014-4.342）。

“在这个分析中，我们已经表明，尽管在几乎所有的患者中实现了病毒学抑制，并且在大多数用[Viread]治疗5年的患者中证明了纤维化消退，但大约1/5的患者未能达到ALT正常化。研究人员得出结论。 “宿主和病毒因子，特别是肝脂肪变性和HBeAg血清阳性是这一现象的重要因素。” - 由Talitha Bennett

披露：Jacobson是AbbVie，Bristol-Myers Squibb，Gilead，Janssen和Merck的顾问，并获得了荣誉并获得了研究支持;并且是Achillion，Alnylam和Enanta的顾问。