Cirrhosis: new research provides a basis for rational and targeted treatments

Abstract

Liver transplantation and antiviral treatments for hepatitis have improved the outlook for many patients with liver disease. For patients with cirrhosis, new developments herald targeted treatments

Fig 1

Liver cirrhosis as wound healing: damage to the normal liver (a) results in inflammation (b) and activation of hepatic stellate cells (brown) to secrete collagen, culminating in the development of fibrosis (c) and ultimately in cirrhosis (d). Withdrawal of the injurious agent may allow remodelling of the fibrillar matrix, leaving an attenuated cirrhosis (e). Spontaneous resolution of fibrosis after removal of injury results in a return to near normal architecture (f). Whether “complete” resolution of cirrhosis can occur is currently unknown

Fig 2

Normal liver (top) and liver injury (bottom). After livery injury, hepatic stellate cells become activated and secrete a collagen rich matrix. Through associated changes in cell-matrix interactions, hepatocytes lose their microvillii and sinusoidal endothelial cells lose their fenestrations. Reproduced with permission

Fig 3

Tissue inhibitors of metalloproteinases (TIMPs) secreted by activated hepatic stellate cells prevent matrix degradation by inhibiting the enzymatic activity of matrix degrading metalloproteinases (MMPs)

Fig 4

Endothelin-nitric oxide imbalance results in contraction of hepatic stellate cells, with consequent sinusoidal constriction (indicated by yellow arrows), contributing to portal hypertension