编者按：非酒精性脂肪性肝病（NAFLD）正威胁着全球约24%的成年人，是一种慢性肝病，后期可发展为肝硬化和肝癌。第68届美国肝病研究学会（AASLD）年会期间，美国Inova Fairfax医院肝脏疾病研究中心Zobair M. Younossi教授代表AASLD介绍了美国的NAFLD疾病负担和诊疗进展。会后，Younossi教授接受了本刊的专访，相关内容如下。

 

成人NAFLD的流行现状？

 

Younossi教授：非酒精性脂肪性肝病（NAFLD）包括一系列疾病，肝脏脂肪堆积合并肝细胞的其他潜在变化，最终可能导致肝脏瘢痕形成（即纤维化），从而导致肝硬化及其并发症。全球NAFLD患病率大概在25%左右。NAFLD患病率最高的地区是中东，最低的是非洲。在东亚国家，NAFLD的患病率也很高（25%～27%）。

 

非酒精性脂肪性肝炎（NASH）是NAFLD疾病谱中易发生疾病进展的类型。不同地区的NASH发生率不尽相同，但总的来说，3%～5%的人患有这种潜在的进行性脂肪性肝病。NASH主要见于有代谢性疾病的患者，尤其是2型糖尿病患者。事实上，如果我们对糖尿病患者进行活检，其中一半以上会有NASH。约15%没有NASH，但是会有明显的肝脏瘢痕。

 

NASH目前的治疗选择？

 

Younossi教授：目前，我们一致推荐的治疗手段是改变生活方式。如果患者肥胖，我们要求他们减肥。糖尿病、高脂血症和高血压都需要得到很好的控制。没有明确的NASH治疗手段。

 

曾经有学者建议，在肝活检确诊的NASH且没有糖尿病或肝硬化的患者中使用抗氧化剂（如维生素E），这样可能会有一定的疗效。另外，如果患者同时患有糖尿病，可以使用吡格列酮这样的药物，这不仅对他们的糖尿病有帮助，而且对NASH也有帮助。除此之外，目前市场上尚没有其他获FDA批准的可用于治疗NASH的药物。

 

临床试验、新药审批进展？

 

Younossi教授：目前有超过25项的II期临床试验正在进行中，另有4项III期临床试验。III期临床试验在预审阶段已显示出较好前景，其中部分方案已获FDA加速审批。大部分药物都展现出良好的应用前景，在这种情况下，我们必须要看到他们能否改善肝纤维化和脂肪性肝炎的最终结果。

 

Hepatology Digest: The clinical and epidemiologic burden of nonalcoholic fatty liver disease（NAFLD） in the adult population of American?

 

Dr.Younossi: Non-alcoholic fatty liver disease is a spectrum of diseases that includes having fat in the liver plus other potential changes in the liver cells that could ultimately lead to scarring of the liver (fibrosis) that could then lead to liver cirrhosis and its complications. The global prevalence of non-alcoholic fatty liver disease is probably around 25%. The highest prevalence of NAFLD is in the Middle East, and the lowest prevalence is in Africa. In East Asian countries, the prevalence of NAFLD is also quite high - around 25-27%. The type of NAFLD that can progress is called non-alcoholic steatohepatitis (NASH). The prevalence of this condition also varies regionally, but in general, about 3-5% will have this potentially progressive form of fatty liver disease. NASH is mostly seen in patients who have metabolic conditions, especially type 2 diabetes. In fact, if we biopsied diabetics, more than half of them would have NASH. About 15% would not have NASH, but would have significant scarring of the liver.

 

Hepatology Digest: What is the current therapeutic options for NASH?

 

Dr.Younossi: Currently, the only therapy that we all recommend is lifestyle modification. If a patient is obese, we ask them to lose weight. Diabetes needs to be well controlled. Hyperlipidemia and hypertension need to be well controlled. But there is no established treatment. There have been suggestions that using antioxidants like vitamin E in patients who have biopsy-proven NASH without diabetes or cirrhosis, then that will probably be beneficial. On the other hand, if you have a patient who is diabetic, you could use a drug like pioglitazone, which may be helpful not only for their diabetes but also NASH. But otherwise, there are no other FDA-approved drugs currently on the market for the treatment of NASH.

 

Hepatology Digest: There is no approved therapeutic options for NASH available, but a large number of clinical trials are underway. What are the most promising ones?

 

Dr.Younossi: There are more than twenty-five phase II clinical trials in progress. There are four phase III clinical trials. The phase III clinical trials have shown promise in terms of being at the pre-approval stage. Some of these are on an accelerated protocol for FDA approval. I can’t say that any drug is going to better than another one, but I can say that most of these drugs do have promise. In that context, we have to see the final results as to whether they improve scarring of the liver and steatohepatitis.