* Liver Cirrhosis

By: Dasol Shin & Priyanka Lian Singh

*Review: What is

Cirrhosis?

* Inflammation and Repair

* Wound healing process is an integral part of overall process of
inflammation and repair

* Liver fibrosis and cirrhosis are both characterized by an increase

in total liver collagen and other matrix protein that impair liver
function

Pathogenesis of fibrosis
Normal liver

Injured liver

* Incoming inflammatory
cell secreting soluble
cytokines

Interleukin-10 is a downregulator of the

inflammatory process
Tumor necrosis factor is
a pro-inflammatory
mediator

* Damaged, regenerating
hepatocyte activating
hepatic stellate cells

Transforming growth
factor -1 promote
fibrosis

*General mechanism
of fibrosis

*Matrix Synthesis

*Matrix Synthesis

* MMPs = Matrix degrading metalloproteinases

* TIMPs = Tissue inhibitors of metalloproteinases 1 & 2
* Rodent testing results
* TIMP expression decreased
* MMP expression is constant
* Therefore, matrix is effectively degraded!!

*Degrading the Matrix

Mechanism mediating activation of stellate cell is unknown

Contractile intracellular protein, smooth muscle actin

Cell is injured

Activated cell is senstive to endothelin

Stellate cell contraction

Increase in portal hypertension

* Stellate cells as mediators of

portal hypertension

Clinical assessment of
antifibrotic interventions
relies on liver biopsies
which is prone to sampling
error
Serum Marker of fibrosis
1. Predict the stage of
fibrosis
2. Monitor disease
progression

*Serum markers of

fibrosis

* http://transplant.surgery.ucsf.edu/conditions-

-procedures/non-alcoholic-fatty-liver-disease.
aspx
* http://ars.els-cdn.com/content/image/1-s2.0S0140673608603839-gr2.jpg
* http://www.medscape.com/content/2002/00/43
/64/436461/art-mgi436461.fig1.jpg

*References