Blood pressure drug reverses liver damage

Jun 1 2009

British scientists have discovered that blood-pressure drugs can reverse the effects of early-stage liver failure in some patients.

The researchers at Newcastle University conducted a small clinical trial of losartan, a drug normally prescribed for hypertension, on 14 patients in Spain, who had Hepatitis C - their illness was at an advanced stage and had caused fibrosis or scarring of the liver - which would usually have progressed to liver failure.

In the early stage trial half of the patients saw the scars in their liver shrink allowing the organ to repair itself.

Professor Derek Mann says currently there is no proven, effective way of treating people with chronic liver disease other than transplantation but the trial has shown that it is possible to shrink liver scarring in some patients and offers the promise of a treatment that could make a huge difference to the lives of thousands of people.

The researchers say the results are promising and they now want to carry out several much larger studies initially involving patients with liver disease caused by obesity and then alcohol and hereditary and autoimmune diseases.

Experts say liver damage, known as fibrosis, is caused by the unwanted accumulation of excess fibrous connective tissue which is produced and maintained by a specialised cell, the liver myofibroblast.

In chronic liver disease a signalling pathway is created that instructs the liver myofibroblast to stay alive and proliferate and it is this process that then causes scar tissue to accumulate, creating the liver damage.

Earlier research carried out in rat and mouse models allowed the researchers to study what was happening inside the liver when losartan, an angiotensin II receptor antagonist drug, was present - the team believe that the drug blocks the signalling pathway so that the liver myofibroblasts die, removing the source of scar tissue and as the scar tissue breaks up, the damaged area of the liver is repaired by the body.

Their research also revealed a biological marker, NF-kB, was crucial for the activities of scar-forming cells - tests on the patients' livers revealed that, before treatment with losartan, half of the patients had a high level of the biomarker NF-kB and after treatment, the level fell indicating that losartan is able to switch off NF-kB with the result that scars are no longer produced or maintained, but instead shrink.

Professor Mann says by measuring the amount of active NF-kB in the liver from a biopsy sample, it may be possible to tell which patients will benefit from treatment with losartan or similar drugs such as ACE inhibitors and this may prove to be a new treatment for up to half of all liver patients.

The trial was carried out with patients at the Liver Unit, Institut Clinic de Malalties Digestives i Mataboliques, Hospital Clinic, Insitut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain.

The research was funded by the Medical Research Council and the British Liver Trust and is published the current issue of Gastroenterology.