编者按：Arun Sanyal博士，美国弗吉尼亚联邦大学医学院胃肠病、肝病和营养科教授，曾任AASLD2010主席，致力于静脉曲张出血、腹水、肝肾综合征、肝性脑病、非酒精性脂肪性肝炎（NASH）等肝病领域的研究。Sanyal教授为国际知名非酒精性脂肪性肝病（NAFLD）专家，NIH大型项目负责人，所完成研究对众多学会相关指南的制订有非常重要的影响。“第三届中国国际肝病论坛”召开期间，Sanyal教授就NAFLD话题接受了《国际肝病》的专访。

 

　　《国际肝病》：过去十年里，NAFLD研究方面有哪些重要进展？

 

　　Arun Sanyal教授：过去的10年里，在疾病进展以及肝纤维发生机制等方面，我们获得了重要的发现，这不仅有助于新药的开发，也有助于疾病的恢复甚至肝硬化的逆转。其中，PIVENS队列研究认为维生素E对于NASH的治疗有效，FLINT研究的结果显示其不仅可以减轻NASH活动程度，而且可以改善肝纤维化程度。

 

　　Prof. Sanyal: I think we have made a lot of progress in this field in virtually every area. We have had important studies that have shown the mechanism by which the disease develops. We have had a lot of progress in the last 10 years. We have had numerous studies that have shown the mechanisms by which the disease develops and progresses to cirrhosis. This has allowed us to find drugs to treat the disease and we have now shown that the disease can be reversed and even the fibrosis can be reduced. Specifically the PIVENS trial showed that vitamin E is very effective in improving NASH and the FLINT trial showed that not only can we reduce NASH activity but also improve fibrosis in the liver.

 

　　《国际肝病》：就膳食调整减肥的效果而言，相同热量的不同饮食之间是否有差异？

 

　　Arun Sanyal教授：这个问题目前还没有形成共识，但我们普遍认为具有相同热量的不同饮食或多或少都会有相似的作用。有一些研究结果显示，地中海型饮食具有较高的多聚不饱和脂肪酸类、鱼产品、新鲜水果等，看似均有益于新陈代谢，且具有抗炎效果，但作为NASH的一种治疗方案，我认为还不够严谨。

 

　　Prof. Sanyal: This has not really been tested in a critical way but our general feeling is that different diets with similar calories have more or less similar effects. There is certainly evidence that the Mediterranean type diet which is high in poly unsaturated fatty acids; fish products, fresh fruits, etc., seem to have a more beneficial effect on the metabolic status and in general have an anti inflammatory effect. Again, this has not been rigorously studied in my view as a treatment of NASH.

 

　　《国际肝病》：是否有膳食补充剂可推荐用于NAFLD患者？

 

　　Arun Sanyal教授：目前市面上有多种膳食补充剂，但是没有足够的科学证据显示任何一种具有优势。需要提醒大家的是，某些补充剂即使是纯天然制成，也可能有毒。入口食品均应谨慎，除了那些已经被证实安全的产品，如绿茶类，很多国家均有销售，普遍认为其安全，且具有抗氧化作用，至少理论上对人体有益。另外，也有一些研究认为咖啡因对人体有益，所以咖啡可能也是安全的产品。

 

　　Prof. Sanyal: There are a lot of dietary supplements that people push but there is no hard evidence and no scientific evidence that any one supplement is better or worse than the others. It is important to remember that certain supplements even though they are natural products can be toxic. There are plenty of things in nature that are poisonous and so we have to be careful about these and unless we are talking about something that is generally widely shown to be safe, we should not engage in these products, specifically I think things like green tea etc which have been consumed for many centuries and generally have been shown to be safe and are known to have some antioxidant properties and at least theoretically one would think that things like that are probably beneficial. Certainly caffeine has been shown in a number of studies to also be beneficial so coffee is probably not a bad thing either.

 

　　《国际肝病》：正在进行或已经完成临床试验评估的许多药物中，哪种是最有前景的NAFLD治疗药物？

 

　　Arun Sanyal教授：现在有很多种药物，很难说哪一种最有前途。目前有两种药物正处于药物审批的最后阶段。其中，奥贝胆酸（一种胆汁酸衍生物）有助于肝脏的修复，但它会引起胆固醇的升高，也会有皮肤发痒等不良反应，所以目前仍存在一些问题。

 

　　此外，目前研发出一类专门针对炎症部位的复合物，看似也很有前景。它完全取决于目标患者的类型：一些促新陈代谢复合物如脂肪酸和胆汁酸的耦联剂对部分早期患者有作用；如牛初乳类作为膳食补充剂可能很有价值；但对于一些进展期的患者而言，就需要一些针对性更强的药物去缓解炎症和肝纤维化程度。吉利德关于泌乳素靶向治疗肝纤维化的最终试验结果，也让我们很期待。

 

　　Prof. Sanyal: I think there are a lot of drugs, it is very hard to say which is the most promising. There are two drugs that are going to the final stages of drug approval. One is obeticholic acidacid which is a bile acid derivative, which has a fantastic profile of benefitting the liver, but it does cause the cholesterol to go up. It causes patients to itch so it has some issues with it. There is another compound targeting inflammatory targets which also looks quite promising. It all depends on what kind of patients are being targeted, if patients are early in the stage of the disease some of the metabolic compounds such as fatty acid and bile acid conjugates will be very beneficial. Drugs like bovine colostrum may be very beneficial which is also probably a dietary supplement in which looks very promising. But for people with more advanced disease you need more targeted therapies directed at inflammation and fibrosis. Gilead has their galactin trials targeting fibrosis; we are very excited about them and looking forward to the results of those trials to see if they actually will deliver on their promise.

 

　　《国际肝病》：对于NAFLD患者的治疗，应该考虑减肥手术吗？

 

　　Arun Sanyal教授：我认为肥胖外科手术对于脂肪肝的效果很小。肥胖症在当今社会相当普遍，外科手术不能很好地解决这个问题。肥胖症手术有很多的不良反应，权衡利弊，我不认为它对于每一位脂肪肝患者来说都是好的选择。然而，如果因为肥胖、糖尿病、睡眠障碍，或者多种并发症而达到肥胖外科手术指征的患者同时存在NASH，那么我认为手术治疗是合理的，但该类患者不能术后立即出院，需要进行较长时间饮食和医疗方面的观察。

 

　　Prof. Sanyal: Yes so bariatric surgery has a very limited role in my view in the treatment of fatty liver disease. This is a disease that affects many people in society and I do not think a surgical is the solution. There are a lot of side effects to bariatric surgery. On the one hand you have to weight the benefits with the risks and the risk benefit ratio does not allow me to say this is a great treatment for everybody with fatty liver disease. However, if someone needs bariatric surgery because they have obesity, diabetes, sleep apnea, or they have multiple comorbidities that are legitimate indications for bariatric surgery and they also have NASH, then I think it is reasonable to proceed to bariatric surgery in that setting but then patients have to be followed properly in the long term. You cannot just operate and tell the patient to go home. They require long term dietary and medical follow up to make sure the patients do well after bariatric surgery.