A blood-pressure medicine has been shown to reverse the effects of early-stage liver failure in some patients.

Newcastle University researchers analysed a small clinical trial of losartan, a drug normally prescribed for hypertension, on 14 patients in Spain, who had Hepatitis C.

The illness was at an advanced stage causing fibrosis - scarring in the liver - which would usually have progressed to liver failure.

Half of the patients in the trial saw the scars in their liver shrink allowing the organ to repair itself.

Professor Derek Mann from Newcastle University said: “At the moment we have no proven effective way of treating people with chronic liver disease other than transplantation. This early stage trial has shown that we can shrink liver scarring in some patients and shows promise for a treatment that could make a huge difference to the lives of thousands of people.”

The team whose work is published today in Gastroenterology, say this early stage trial is promising and they now want to carry out several much larger studies initially involving patients with liver disease caused by obesity and then later alcohol, hereditary and autoimmune diseases.

Mechanism

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. It is this pathway that then causes scar tissue to accumulate, creating the liver damage.

Work 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.

Researchers believe that the drug blocks the signalling pathway so that the liver myofibroblasts die, removing the source of scar tissue. As the scar tissue breaks up, the damaged area of the liver is repaired by the body.

In this research, funded by the Medical Research Council and the British Liver Trust, the Newcastle University researchers discovered a biological marker, NF-kB, was crucial for the activities of scar-forming cells.

Tests on their livers revealed that, before treatment with losartan, half of the patients had a high level of the biomarker NF-kB. 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 said: “By measuring the amount of active NF-kB in the liver from a biopsy sample, we may be able to tell which patients will benefit from treatment with losartan or similar drugs such as ACE inhibitors. 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.

Paper: Angiotensin II activates IkB kinase phosphorylation of Re1A at Ser536 to promote myofibroblast survival and liver fibrosis

Authors: Fiona Oakley, Victoria Teoh, Gemma Ching-A-Sue, Ramon Bataller, Jordi Colmenero, Julie R Jonsson, Aristides G Eliopoulos, Martha R Watson, Derek Manas, Derek A Mann.

Source:
Karen Bidewell

Newcastle University

WASHINGTON, June 3 — The FDA today warned physicians that a drug used for 62 years to treat Graves’ disease — propylthiouracil, or PTU — carries an increased risk for life-threatening liver injury.

The FDA said it has received 32 adverse event reports — 22 in adults and 10 in children — including 12 deaths and six transplants among adult users of the medication. In the pediatric population, the FDA said there were one death and six transplants linked to PTU use.

“Physicians should closely monitor patients on PTU therapy for symptoms and signs of liver injury, especially during the first six months after initiation of therapy,” the FDA said.

The agency said that when PTU, which was approved in 1947, was compared with methimazole (MMI), approved in 1950, there was evidence of excess hepatotoxicity linked to PTU.

Among MMI users, the FDA identified five reports of serious liver injury. All five cases — including three deaths — were in adult patients.

Both drugs are approved for treatment of hyperthyroidism due to Graves’ disease, and the FDA advised physicians to “carefully consider which drug to initiate in a patient recently diagnosed with Graves’ disease.”

In general, PTU is considered second-line therapy except in patients who are allergic to or intolerant of MMI.

According to the FDA there have been rare cases of embryopathy, including aplasia cutis, reported with use of MMI during pregnancy, while no such cases have been reported with PTU use. For that reason, the FDA said, PTU might be more appropriate for patients who are in their first trimester of pregnancy.

Today’s warning followed a public workshop on PTU hepatotoxicity held by the FDA and the American Thyroid Association in April.

The FDA said it would continue to monitor PTU and update its label if needed. Meanwhile, the thyroid association has announced plans to update its treatment guidelines for Graves’ disease.

Registration forms for the prereg trainee pharmacist programme 2009/10 are now available to download on the NPA members’ website. The NPA is also providing training on 26 June 2009 for prereg tutors that have enrolled their prereg on to the NPA’s programme.

Sabina Khanom, Assistant Head of NPA Education and Training said: “We would encourage all prereg tutors to attend the training day on 26 June in St Albans, especially those tutors who are new to prereg training. The session will cover the role of a prereg tutor, performace standards, performance review & feedback and dealing with problems that may be encountered whilst tutoring a prereg.”

The 2008/9 prereg trainee pharmacists completed the programme on 24 April 2009 with Ramesh Yadev from Northway Pharmacy in the West Midlands winning the audit project prize. Ramesh said: “The NPA prereg programme provided me with a thorough revision of the exam syllabus. I feel much more confident now for the exams. The session on the Drug Tariff and Measuring & Fitting Hosiery was particularly excellent.”

The investment price for the course is £1,500 + VAT including resources and accommodation during courses. The study courses will be held in three locations - St Albans, Birmingham and Wakefield. The closing date for bookings is 7 September 2009. To download the application form members log on to: http://www.npa.co.uk/members/education_and_training_pt.php.

Source
National Pharmacy Association