Liver cirrhosis
Liver cirrhosis
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DOI：
10.1016/j.bpg.2011.02.009
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发表时间：
2011-04-01
影响因子：
3.2
通讯作者：
Zuckermann, Michele
中科院分区：
文献类型：
--
作者：
Pinzani, Massimo;Rosselli, Matteo;Zuckermann, Michele
肝硬化是所有慢性肝病长期临床病程的常见结果，其特征在于组织纤维化和正常肝脏结构转化为结构异常结节。门脉高压是肝硬化最早和最重要的后果，是该疾病的大多数临床并发症的基础。门静脉高压是肝内阻力增加和门静脉（和肝动脉）血流量增加的结果。肝组织的纤维化和血管结构改变导致肝内阻力增加和门静脉高压的程度似乎高度相关，直到HVPG值达到10-12 mm Hg。在这一阶段，广泛代表了“代偿性”和“失代偿性”肝硬化之间的转折点，额外的肝外因素制约了PH的进一步恶化。事实上，HVPG >= 10-12 mm Hg代表了一个临界阈值，超过该阈值，慢性肝病就变成了一种累及其他器官和系统的全身性疾病。肝脏的基本功能之一的进行性失效，即从内脏循环接收的潜在有害物质和特别是细菌终产物的解毒，是建立全身促炎状态的原因，进一步加速疾病进展。肝硬化的生物学特征是在以慢性炎症和组织纤维化为特征的微环境中持续刺激肝细胞再生，因此代表了诱发肝细胞癌（HCC）发展的理想条件。在过去的20年里，肝硬化并发症的治疗有了显著的改善，HCC正在成为导致患者死亡的最常见的临床事件。尽管有证据清楚地表明，肝硬化前疾病的纤维化是可逆的，但肝硬化中纤维化消退的决定因素还不够清楚，肝硬化真正不可逆的点还没有建立，无论是在形态学上还是在功能上。因此，肝硬化患者抗纤维化治疗的主要终点应该是减少肝硬化背景下的纤维化，对门脉高压和HCC的出现产生有益的影响。(C)2011爱思唯尔有限公司保留所有权利。
Liver cirrhosis is a frequent consequence of the long clinical course of all chronic liver diseases and is characterized by tissue fibrosis and the conversion of normal liver architecture into structurally abnormal nodules. Portal hypertension is the earliest and most important consequence of cirrhosis and underlies most of the clinical complications of the disease. Portal hypertension results from an increased intrahepatic resistance combined with increased portal (and hepatic arterial) blood flow. The fibrotic and angio-architectural modifications of liver tissue leading to increased intrahepatic resistance and the degree of portal hypertension seem to be highly correlated until HVPG values of 10-12 mm Hg are reached. At this stage, which broadly represents the turning point between 'compensated' and 'decompensated' cirrhosis, additional extra-hepatic factors condition the further worsening of PH. Indeed, a HVPG >= 10-12 mm Hg represents a critical threshold beyond which chronic liver disease becomes a systemic disorder with the involvement of other organs and systems. The progressive failure of one of the fundamental functions of the liver, i.e. the detoxification of potentially harmful substances received from the splanchnic circulation and particularly bacterial end-products, is responsible for the establishment of a systemic pro-inflammatory state further accelerating disease progression. The biology of liver cirrhosis is characterized by a constant stimulus for hepatocellular regeneration in a microenvironment characterized by chronic inflammation and tissue fibrosis, thus representing an ideal condition predisposing to the development of hepatocellular carcinoma (HCC). In reason of the significant improvements in the management of the complications of cirrhosis occurred in the past 20 years, HCC is becoming the most common clinical event leading to patient death. Whereas evidence clearly indicates reversibility of fibrosis in pre-cirrhotic disease, the determinants of fibrosis regression in cirrhosis are not sufficiently clear, and the point at which cirrhosis is truly irreversible is not established, either in morphologic or functional terms. Accordingly, the primary end-point of antifibrotic therapy in cirrhotic patients should be the reduction of fibrosis in the context of cirrhosis with a beneficial impact on portal hypertension and the emergence of HCC. (C) 2011 Elsevier Ltd. All rights reserved.