[Hepatology] Reversing liver cirrhosis

Research suggests that the fibrosis can be removed from the liver, clearing the way for regeneration of healthy liver cells to occur. Can liver cirrhosis be reversed?

In response to chronic inflammatory signals, including cytokines and reactive oxygen species, hepatic stellate cells (HSC) awaken from a quiescent state and differentiate into myofibroblasts. Exposure to apoptotic hepatic cells is also known to trigger activation. Myofibroblasts initiate hepatic fibrogenesis. HSCs deposit type 1 collagen fibers, damaging hepatic cells and vasculature.

Over time the liver shrinks and fills with collagen. The loss of useful hepatic cells results in a decline in liver function. The liver function tests (LFTs) show reduced albumin synthesis. Coagulation screening (PT, INR, APTT, fibrinogen) reveal prolonged bleeding times.

However, it is known that myofibroblasts can receive further signals, which convert them to inactive HSCs, or trigger apoptosis. It has been demonstrated that the elinination of myofibroblasts leads to the regression of fibrosis.

Many compounds have been developed which target these pathways and promote the regression of fibrosis. For example:

1. Cannabinoid receptor 1 (CB1) is upregulated on myofibroblasts and CB1 signalling is known to have a pro-fibrotic effect. The inhibition of CB1 leads to the inhibition of HSCs . 
2. CCR1/CCR5 antagonists have been shown to promote hepatocyte survival, while inhibiting HSCs.

There are several clinical trials underway to prove that these drugs are safe and efficacious for patients with liver cirrhosis.