本帖最后由 StephenW 于 2012-5-7 18:26 编辑
Clinical evidence for the regression of liver fibrosisInstitute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK Received 15 April 2011; received in revised form 15 September 2011; accepted 27 September 2011. published online 16 January 2012.
Summary
Fibrosis is a common pathological process for the majority of liver
diseases which in a significant minority of patients leads to endstage
cirrhosis and/or hepatocellular carcinoma. Data emerging
from small rodent models of chronic liver disease have demonstrated
that fibrotic extracellular matrix can be remodelled and
near-normal hepatic architecture regenerated upon cessation of
injury. Moreover, regression of liver fibrosis in these model systems
can be stimulated with drugs that target the activities of
fibrogenic hepatic stellate cells. These findings are exciting as
they suggest that established fibrosis is susceptible to regression
and possibly even reversion. Alongside these experimental studies
is a growing body of clinical data that suggest regression of
fibrosis may also occur in liver disease patients for whom an
effective treatment is available for their underlying liver injury.
This paper provides an up-to-date review of the currently available
clinical data and also considers technical caveats that highlight
the need for caution in establishing a new dogma that
human liver fibrosis is reversible.
Introduction
The burden of chronic liver disease is rising in the UK and worldwide.
Whilst viral hepatitis remains the leading cause of liver transplantation
globally, the prevalence of non-alcoholic fatty liver
disease (NAFLD) has escalated over the last decade and is increasingly
being recognised as a cause of liver cirrhosis and hepatocellular
carcinoma (HCC) [1,2]. A common pathological feature of
chronic liver disease is fibrosis which results from unregulated
wound-healing and is characterised by the progressive replacement
of functional hepatic tissue with highly cross-linked collagen
I/III-rich extracellular matrix. Fibrosis perturbs both the normal
architecture and functions of the liver especially in the end-stage
of cirrhosis. Fibrosis is also considered a pre-cancerous state that
provides microenvironments in which primary tumours may
develop. The dogma prevailing in the literature until recently was
that fibrosis is irreversible and the best hope therapeutically would
be to halt progression.However, there is now mounting clinical evidence
that liver fibrosis can regress in a variety of liver diseases,
observed either on cessation of the cause of liver injury or treatment
of the underlying disease. Significant advances in our understanding
of the pathogenesis of liver fibrosis have enabled the
identification of potential therapeutic targets but as yet, there are
no licensed anti-fibrotic therapies [3]. If fibrosis is genuinely a
reversible state then the scene is set for clinical trials that determine
the ability of anti-fibrotics to promote fibrosis regression.
Key Points
• There is increasing clinical evidence for the regression of
improved clinical outcomes
• Histological evaluation through liver biopsy remains the
impractical for repeated measures; combining
non-invasive technologies, in conjunction with hard clinical
outcomes, will be important in longitudinal evaluation of
future treatment trials
• There is a real need for standardised reporting methods to
liver fibrosis in a variety of liver diseases associated with
reference standard for assessing liver fibrosis but is
aid interpretation of anticipated anti-fibrotic therapy trials | 
发表于 2012-5-7 18:25
