Pathogenesis and treatment of hepatic fibrosis: is cirrhosis reversible?

StephenW

CME Hepatology Clinical Medicine 2011, Vol 11, No 2: 179–83
Pathogenesis and treatment of hepatic fibrosis: is cirrhosis reversible?
Jonathan Fallowfield, Academy of Medical Sciences/Health Foundation
clinician scientist and honorary consultant hepatologist;
Peter Hayes, professor of hepatology
University of Edinburgh
Fibrosis, or scarring, of the liver is a generic wound healing response to
chronic liver disease regardless of aetiology.
Progressive fibrosis eventually evolves to cirrhosis, with fibrotic bands,
parenchymal nodules and vascular distortion leading to liver cell dysfunction,
portal hypertension (PHT), hepatocellular carcinoma (HCC) and premature death.
Liver fibrosis is a clinically silent process, such that many patients present at an
advanced stage when disease-specific therapy has limited impact.
Central to this is the recognition that cirrhosis is not simply severe fibrosis but a more complex pathological condition with reversible and irreversible components.
Detailed analysis of the cellular and molecular mechanisms that mediate liver
fibrosis has provided a framework for therapeutic approaches to prevent, slow or
even reverse fibrosis or cirrhosis.
The goal of such treatments would be stasis or regression of fibrosis to precirrhotic stages to prevent the development of liver failure, HCC and/or to reduce PHT and its complications such as variceal haemorrhage, ascites and encephalopathy.
Despite this rationale, no antifibrotics are currently licensed for use in humans.
Epidemiological projections for the future prevalence of viral, obesity and alcohol-related cirrhosis paint an increasingly gloomy picture.
Together with a shortfall in donors for liver transplantation, the clinical urgency for new therapies is high.1 There is increasing interest from stakeholders keen to exploit the market potential for antifibrotics. The design of future trials for agents in the developmentalpipeline will depend upon:
• strategies to ensure equal patient stratification
• techniques to reliably monitor changes in fibrosis over time
• definition of clinically meaningful end-points.

StephenW

CME肝病临床医药2011年第11卷，2：179-83
肝纤维化的发病机理和治疗：肝硬化是可逆的？
乔纳森法洛菲尔德，医学/健康基金会学院,临床医师科学家和名誉顾问肝病;
肝病学教授彼得海耶斯，爱丁堡大学

纤维化或疤痕化的肝脏，是一个通用的伤口愈合反应, 慢性肝病不论病因。
进纤维化，最终发展为肝硬化，纤维化乐队，实质结节和血管扭曲，导致肝细胞功能障碍，
门脉高压症（PHT），肝细胞癌（HCC）和过早死亡。
肝纤维化是一个无临床症状的过程，例如，很多病人在一个目前先进的阶段时，特定疾病治疗的影响有限。
这是中央承认，肝硬化是不是简单的严重纤维化，但更复杂的可逆和不可逆元件的病理状态。
详细分析，介导肝细胞和分子机制 纤维化的治疗方法提供了框架，以防止，减缓或 甚至逆转肝纤维化或肝硬化。
这种治疗方法的目标将瘀或回归纤维化 precirrhotic 阶段，以防止肝功能衰竭，肝癌和/或减少苯妥英钠及其并发症，如静脉曲张破裂出血，腹水和脑病的发展。
尽管这样做的理由，目前没有antifibrotics 许可使用在人类身上。
流行病学预测未来的流行病毒，肥胖和酒精相关的肝硬化涂料日益黯淡的画面。
连同在肝移植捐赠者的短缺，新疗法的临床紧迫感high.1有越来越多的来自利益相关者热衷于利用市场潜力为antifibrotics的利益。 developmental pipeline代理人的未来试验的设计将取决于：
•战略，以确保平等的病人分层
•可靠地监控技术随着时间的推移纤维化的变化
•定义的临床意义的终点。

StephenW

Key Points:

The hepatic scar is dynamic with respect to cell and matrix components; myofibroblasts
(MFs) and hepatic macrophages are key players in progression and regression of
fibrosis.
Loss of fibrogenic MFs is a pivotal event in fibrosis regression, allowing spontaneous
degradation of scar.
There is evidence for fibrosis regression in cirrhosis, but not for reversal.
Therapies that directly target hepatic stellate cell-MFs, degrade scar or stimulate liver
regeneration are poised to enter the clinical arena.
Lack of robust, standardised treatment end-points is currently the major limiting factor
in antifibrotic trials.

关键点：

肝疤痕是动态的，细胞和基质成分;肌纤维母细胞（MFS）和肝巨噬细胞的进展和回归的关键球员 纤维化.
纤维化微丝的损失是在回归纤维化的关键事件，允许自发瘢痕退化.
有肝硬化纤维化回归的证据，但不能逆转.
治疗直接针对肝星状细胞- MFS，降低瘢痕或刺激肝再生正准备进入临床舞台.
缺乏强大的，规范化的治疗终点是目前的主要限制因素在抗肝纤维化试验.

StephenW

咬牙硬挺

哈哈肝纤维化都有救了啊

StephenW