《国际循环》:联合降脂治疗时,如果出现肝功能损害,您是首选停用他汀类药物还是贝特类药物?
Elam教授:我想你是指联用贝特类和他汀类药物的患者出现肝酶升高。我想两者都可能引起肝酶升高。已知贝特类和他汀类药物都会导致该不良反应。但是,如果你让我选择一种物的话,应该是哪种药物呢?如果患者的肝酶显著升高,我想处理方法就是停用这两种药物,然后观察和评价患者,再重新开始用其中一种药物治疗。我真的认为,我们没有办法来预测。我想,这取决于患者。如果患者的主要问题是低密度脂蛋白胆固醇高(LDL-C),同时心血管风险较高,我想说他汀比贝特类药物更为重要。另外,如果患者表现为明显的高甘油三酯血症,发生胰腺炎的风险很高时,那么贝特类是更为重要的药物。但是,我认为,主要问题是要意识到接受降脂药物治疗的任何一位患者肝酶持续性升高都应当找到原因,在很多病例可能是由于与药物完全无关的情况。例如患者可能在饮酒,但是却不承认。在很多情况下,如果患者超重同时又有高甘油三酯血症的话,患者的肝脏可能有脂肪浸润,肝脏甘油三酯水平很高,可能导致脂肪肝。在这些存在脂肪肝的患者中,治疗高脂血症能够对肝酶产生有益的影响。因此,我认为对于医生来讲,很重要的是评估患者,在必要时让患者去消化科就诊。要思考“患者到底怎么了?”、“其原因是什么?”。因为在很多情况下,是其他原因而不是降脂药物本身导致了肝酶的升高。就ACCORD血脂研究来讲,在他汀联合贝特类药物治疗组,转氨酶水平升高的患者比例要比单药治疗组稍高。但是,我想这并不一定意味着贝特类和他汀类药物存在相互作用,而是贝特类和他汀类药物在某些患者单独可以导致肝酶的升高。我记得,ACCORD血脂研究中肝酶升高的发生率很低,还不到0.5%。
<International circulation>:If dysfunction of liver came out when using intensive lipid lowering treatment, what is yours choice ,stop using the Fibrates or the Statin?
Dr Elam KEN:As I understand it, this question refers to a patient who is on combination therapy, with fibrate and statin, and develops elevated liver enzymes. And I think either one would be suspect, as far as causing elevated liver enzymes. It’s a known side effect of both the fibrates and the statins. If it is a significant elevation in liver enzymes, I think the trick would be to just continue both of them, and then evaluate the patient and restart one or the other. I really think there will be no way to predict.Well, it depends on the patient. If it is a patient whose primary problem is LDL and high risk for cardiovascular disease, I would say that statin would be the more important of the two. On the other hand, if it is a patient with extreme hypertriglyceridemia, who is at risk for pancreatitis, for example, then the fibrate would be the agent that would be more important. But I think the main thing is to be aware that any chronic persistent elevation in liver enzymes in a patient that is on cholesterol-lowering therapy needs to be explained, and in many cases it may be due to something completely unrelated. The patient may be drinking alcohol and not admitting it; very often, if the patient is over-weight and hypertriglyceridemic they will have fatty infiltration of the liver, where the liver is filled with triglyceride, which can cause hepatic steatosis. In cases like that where there is hepatic steatosis, actually treating the lipid can also have a favorable effect on the liver enzymes. So I think it’s important for a practitioner to evaluate these patients, and if necessary refer them to a gastrointestinal specialist, and ask the question “what is going on?” “what is causing this?”, because more often than not, it’s actually something else rather than the cholesterol medication. Now in the ACCORD study, we did see a slightly higher incidence of elevated transaminases in the group that was on combination therapy with statin plus fenofibrate. I think that doesn’t really mean there is an interaction, but rather just that fenofibrate itself, as with the statins, is known to elevate liver enzymes in some patients. It was very small as I recall. It was less than half a percent of the patients.