脂肪肝已经成为全球最流行的肝脏疾病，也是第58届欧洲肝脏研究学会年会（EASL2023）暨2023年EASL大会（EASL Congress 2023）的热议话题。《国际肝病》报道团队有幸在大会现场邀请到“Current therapeutic landscape in NAFLD and perspectives”专题主题报告专家、法国巴黎PitiéSalpetriere医院Raluca Pais教授为我们介绍非酒精性脂肪性肝病（NAFLD）的当前治疗手段，特别是减肥治疗的方法和获益，以及新药研发前景和无创评估应用前景。
 

 

《国际肝病》

减肥治疗对于改善非酒精性脂肪性肝病（NAFLD）有非常积极的作用。从目前研究看，减肥治疗总体可带来哪些获益？

 

Raluca Pais教授：我认为减重治疗实际上是NAFLD管理的基石，特别是在缺乏经批准的治疗选择和药物治疗NAFLD的情况下。减重对心血管代谢状况以及肝脏损伤的组织学和严重程度都有明显的益处。而且，减重对肝脏损伤的严重程度的影响可能因减少的重量的不同而有所差异，临床研究已经证实存在一种剂量效应关系。例如，减重5%至7%可以实现NASH某种程度的逆转。至少需要减重10%才能在纤维化逆转方面获得一些益处。

 

然而，NAFLD患者很难实现减重，因为他们大多数是老年人，多患有病态肥胖和与肥胖相关的并发症，如机械性或代谢性糖尿病、睡眠呼吸暂停等。因此，对这些患者来说，进行定期的体育活动和减重可能会很困难。

 

I consider that the weight loss therapy is actually the cornerstone in the management of NAFLD, especially in the absence of approved therapeutic option, approved drug for treatment of NAFLD. There is a clear benefit of the weight loss, both on the cardio metabolic condition, but also on the histology and severity of the liver damage. And then the impact on the severity of the liver damage can differ according to the amount of weight loss, and a kind of dose effect relationship has been evidenced from clinical studies that have been published. For example, 5 to 7 % weight loss can be associated with some regression of NASH. And at least 10 % weight loss is required to have some benefit on fibrosis regression.

 

However, what we should have in mind is that the weight loss is difficult to obtain in patients with NAFLD as most of them are older person and have a morbid obesity and some obesity associated comorbidities, either mechanic or metabolic types of diabetes, sleep apnea, et cetera. And for this reason, performing a regular physical activity and obtaining a weight loss can be difficult for these patients.

 

《国际肝病》

目前有哪些减肥治疗方法？

 

Raluca Pais教授：减重方法包括体育活动、饮食调整、药物疗法和减重手术。

 

There are several ways to achieve weight loss. So this can be achieved through physical activities through dietary changes, or we have pharmacological therapy and bariatric or metabolic surgery.

 

《国际肝病》

当前有大量的NASH新药研究在进展，能否请您谈谈总体进展，哪些研究和新药较具前景？

 

Raluca Pais教授：在NASH患者的药物研发方面目前取得了很大进展。一些正在进行临床前试验的药物可能会获批。其中一些已经在市场上流通，但是用于其他疾病的适应症。另一些药物是专门针对NASH患者开发的。未来，联合治疗可能会成为治疗这些患者的趋势。

 

There has been a lot of progress in the drug development in patients with NASH. And probably that some of the drugs that are now tested in face preclinical trial will get approval. Some of them are already on the market with other indication than NFLD. Some other have been developed and are specific to patients with NASH. And probably that combination therapy will be the future in these patients.

 

《国际肝病》

非侵入性评估在NAFLD有较广泛的应用。对于NAFLD治疗患者，是否也可以用非侵入性标志物来评估疗效呢？请您谈谈这方面的进展和观点。

 

Raluca Pais教授：我认为非侵入性标志物可能会在日常临床实践中使用，因为如果这些药物上市，我们则无法使用肝活检来评估治疗反应。所以我们得使用非侵入性方法，其中一些方法也已作为NASH临床试验的次要终点进行评估。

 

I think that probably the non-invasive marker will be used in everyday clinical practice, because if these drugs get on the market, we cannot use liver biopsy to assess the treatment response. So we have to use non-invasive methods. And some of them has also been evaluated as a secondary endpoint in NASH clinical trials.

 

《国际肝病》

最后，对于NAFLD的治疗，您认为目前仍面临哪些困境，您怎么看未来前景？

 

Raluca Pais教授：我认为困难在于患者的异质性，最终导致治疗反应的异质性。单一药物的使用或许不足以达到治疗效果，应该采用多种途径的联合治疗来增强治疗反应。另一个困难是缺乏可靠的非侵入性标志物来评估治疗反应。

 

I think that the difficulty is that the patient heterogeneity, which finally results a in heterogeneity of treatment response. And probably that using one drug, is not enough. We should use a combination therapy targeting a multiple pathway to enhance the therapeutic response. Another difficulty is that the lack of reliable non invasive markers to assess the therapeutic response.

 

 

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