NAFLD患者死亡危险因素仍然不明

奥兰多——在消化疾病周(DDW)上公布的一项研究显示，非酒精性脂肪性肝病(NAFLD)患者的死亡因素包括老年、男性、躯干性肥胖和高密度脂蛋白胆固醇(HDL-C)水平低，换言之，与心血管疾病死亡和其他原因死亡的危险因素相同。另一方面，NAFLD患者的丙氨酸转氨酶(ALT)水平升高与死亡或其他不良结局风险增加无关，这意味着研究者需更深入地对现有数据进行挖掘，以寻找NAFLD独有的危险预测因素。

Naga P. Chalasani博士

在这项研究中，印第安纳大学的Naga P. Chalasani博士及其同事从第三次全美健康与营养调查(NHANES Ⅲ)中收集了1988~1994年间14,797例20~74岁成人的基线及随访胆囊超声和肝脏影像学数据。研究者将这些数据与全国死亡指数进行关联，以确定NAFLD患者(相对于对照者)早期死亡的危险因素。

研究者将NAFLD定义为：超声检查显示存在中至重度肝脂肪变性，并且无铁过载、乙肝或丙肝病毒感染和过量饮酒。对照者为同一数据集中无基础性肝病且超声检查正常和肝功能检查正常的参与者。

该研究共纳入2,441例NAFLD患者和8,423名对照者。在中位随访14.3年期间，14%(1,193例)的对照者和21%(501例)的NAFLD患者死亡，该差异在单因素分析中具有显著性(P=0.0328)。研究者对总体死亡、癌症相关死亡和心血管死亡进行分析发现，这3个类别的独立死亡预测因素均为男性、老年和HDL-C水平低，不过心血管死亡的额外危险因素还包括代谢综合征。

Keith Lindor博士

Chalasani博士表示，在确定NAFLD患者危险因素的工作中，第一步是识别具有不良结局风险的NAFLD患者。会议主持人Keith D. Lindor对此表示认同，指出目前尚难以轻易定义NAFLD，惯常使用的ALT指标或许也并不能透露太多信息，并且由于脂肪变性需达到一定程度才可被超声检出，因此目前对于超声能在多大程度上有效检测NAFLD尚存有疑问。目前尚不知道活检发现但超声检查未发现脂肪变性的患者是否与肉眼检查发现脂肪变性的患者具有相似的危险因素。

研究者未披露该研究的资金来源。Chalasani博士和Lindor博士均声明无相关经济利益冲突。

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By: NEIL OSTERWEIL, Clinical Endocrinology News Digital Network

ORLANDO – The risk factors for death in patients with nonalcoholic fatty liver disease include older age, male sex, truncal obesity, and a low HDL cholesterol level – in other words, the same factors that increase risk for death from cardiovascular disease and other causes, according to Dr. Naga P. Chalasani.

On the other hand, elevations in alanine aminotransferase (ALT) levels in patients with NAFLD are not associated with an increased risk for death or other poor outcomes, meaning that researchers may have to burrow more deeply through the available data to find risk predictors unique to NAFLD, said Dr Chalasani of Indiana University, Indianapolis.
 
"How do we identify someone with NAFLD who is at risk for poor outcomes? I think this is the first shot at risk mapping patients," Dr. Chalasani said at the annual Digestive Disease Week.

Dr. Keith D. Lindor, who moderated the session at which the data were presented, agreed.

"What we’re having trouble with, I think, is defining nonalcoholic fatty liver disease easily, particularly amongst the population," he said. "We saw data that ALT, which we commonly used to use, may not be telling, and there are questions about how well ultrasound detects [NAFLD], particularly given that the amount of steatosis in order to be detected by ultrasound has to be relatively dramatic."

It is still not known whether people with steatosis discovered during biopsy but not visible on ultrasound will have risk factors similar to those of people with more grossly evident steatosis, he said in an interview.

Although Dr. Chalasani and colleagues failed to find unique risk markers in this population, it was not for want of trying. The investigators pored over data from the third National Health and Nutrition Examination Survey (NHANES III) for baseline and follow-up information about patients with NAFLD.

The data were collected from 1988 through 1994, and included gallbladder ultrasound with liver images in 14,797 adults aged 20-74. The authors linked the data to the National Death Index in an attempt to determine which factors might be harbingers of early mortality in patients with NAFLD vs. controls.
 
They defined NAFLD by the presence of moderate to severe hepatic steatosis on ultrasonography, and by the absence of iron overload, hepatitis B or C infections, and excessive alcohol consumption. Controls were participants in the same data set who did not have underlying liver disease and had normal ultrasound and liver function tests.

There were a total of 2,441 people with NAFLD and 8,423 controls. During a median follow-up of 14.3 years, 14% of controls (1,193), and 21% of those with NAFLD (501) died, a difference that was significant in a univariate analysis (P = .0328).

But when they looked at overall mortality, cancer-related mortality, and cardiovascular mortality, they found that all three categories shared male sex, older age, and a low HDL level as independent predictors for death, with cardiovascular mortality having the added bonus of the metabolic syndrome as an additional risk factor.

The authors did not disclose a funding source. Dr. Chalasani and Dr. Lindor reported having no relevant financial disclosures.