PDF(Pubmed)
Abstract：
Portal hypertension (PH) has traditionally been observed as a consequence of significant fibrosis and cirrhosis in advanced non-alcoholic fatty liver disease (NAFLD). However, recent studies have provided evidence that PH may develop in earlier stages of NAFLD, suggesting that there are additional pathogenetic mechanisms at work in addition to liver fibrosis. The early development of PH in NAFLD is associated with hepatocellular lipid accumulation and ballooning, leading to the compression of liver sinusoids. External compression and intra-luminal obstacles cause mechanical forces such as strain, shear stress and elevated hydrostatic pressure that in turn activate mechanotransduction pathways, resulting in endothelial dysfunction and the development of fibrosis. The spatial distribution of histological and functional changes in the periportal and perisinusoidal areas of the liver lobule are considered responsible for the pre-sinusoidal component of PH in patients with NAFLD. Thus, current diagnostic methods such as hepatic venous pressure gradient (HVPG) measurement tend to underestimate portal pressure (PP) in NAFLD patients, who might decompensate below the HVPG threshold of 10 mmHg, which is traditionally considered the most relevant indicator of clinically significant portal hypertension (CSPH). This creates further challenges in finding a reliable diagnostic method to stratify the prognostic risk in this population of patients. In theory, the measurement of the portal pressure gradient guided by endoscopic ultrasound might overcome the limitations of HVPG measurement by avoiding the influence of the pre-sinusoidal component, but more investigations are needed to test its clinical utility for this indication. Liver and spleen stiffness measurement in combination with platelet count is currently the best-validated non-invasive approach for diagnosing CSPH and varices needing treatment. Lifestyle change remains the cornerstone of the treatment of PH in NAFLD, together with correcting the components of metabolic syndrome, using nonselective beta blockers, whereas emerging candidate drugs require more robust confirmation from clinical trials.
摘要：
传统上已观察到门静脉高压症（PH）是晚期非酒精性脂肪性肝病（NAFLD）中严重纤维化和肝硬化的结果。然而,最近的研究提供了证据，表明PH可能在NAFLD的早期阶段发展，这表明，除了肝纤维化之外，还有其他致病机制在起作用。NAFLD中PH的早期发展与肝细胞脂质积累和膨胀有关，导致肝窦受压。外部压缩和腔内障碍引起机械力，如应变，剪切应力和升高的静水压力，进而激活机械传导途径，导致内皮功能障碍和纤维化的发展。肝小叶的门静脉周围和窦周围区域的组织学和功能变化的空间分布被认为是NAFLD患者PH的窦前成分的原因。因此，目前的诊断方法如肝静脉压力梯度（HVPG）测量倾向于低估NAFLD患者的门静脉压力（PP），他们可能在低于10mmHg的HVPG阈值时失代偿，传统上被认为是临床上有意义的门静脉高压症（CSPH）的最相关指标。这在寻找可靠的诊断方法以对该患者群体的预后风险进行分层方面带来了进一步的挑战。理论上,由内窥镜超声引导的门静脉压力梯度的测量可以通过避免前正弦分量的影响来克服HVPG测量的局限性。但需要更多的研究来测试其临床实用性。肝脏和脾脏硬度测量结合血小板计数是目前诊断CSPH和需要治疗的静脉曲张的最佳验证的非侵入性方法。生活方式的改变仍然是NAFLD治疗PH的基石，以及纠正代谢综合征的成分，使用非选择性β受体阻滞剂，而新出现的候选药物需要更有力的临床试验确认.
