Clinical

Genetic analysis might predict response to losartan in portal hypertension

Last Updated: 2004-05-12 15:30:30 -0400 (Reuters Health)

By Mat�as A. Loewy

BUENOS AIRES (Reuters Health) - Only half of patients with cirrhosis and portal hypertension respond to the antihypertensive losartan, but a simple genetic test might identify those patients who are more likely to improve with the drug, researchers reported here at the XI Argentine Congress of Hypertension.

Dr. Silvia Sookoian, Dr. Carlos Pirola and other cardiologists of the University of Buenos Aires Medical Research Institute Alejandro Lanari found that patients carrying a certain genotype of the angiotensin II type 1 receptor (AT1R) had a 70% chance of success when treated with losartan. On the other hand, presence of other genotypes was linked to an almost 90% chance of failure.

"It's the first genetic marker of pharmacologic response in portal hypertension," Dr. Sookoian said.

In the study, 23 patients with cirrhosis and esophageal varices were treated with losartan 25 mg/day. They were considered to be responders if their hepatic venous pressure gradient (HVPG) was reduced more than 20% after 3 months.

Eleven patients responded. After analyzing several genes involved with the renin-angiotensin system and drug metabolism, researchers found that the A1166C polymorphism of the AT1R gene was the greatest contributor to the efficacy of the treatment. A homozygous A1166 genotype "has a positive and negative predictive value for response of 69.6 and 87.5%," the authors said.

The test uses PCR-restriction fragment length polymorphism analysis and takes less than 4 hours. "It prevents wasting your time. If you are aware that your patient is unlikely to respond to losartan, you can try alternative treatments, such as sclerotherapy for esophageal varices," Dr. Sookoian told Reuters Health.

Angiotensin II may be involved in the pathogenesis of portal hypertension in cirrhosis, according to the authors. For example, circulating angiotensin II makes certain liver cells (hepatic stellate cells) acquire contractile properties and raise hepatic venous pressure. Both effects might be blocked by losartan and maybe other AT1R-blockers.

The new predictive test might reinforce the role of losartan as a safe alternative drug for the long-term treatment of portal hypertension, Dr. Sookoian said. Beta-blockers are traditionally used to prevent bleeding, but their response rate is only 10-40% and side effects limit their prescription in patients suffering from asthma, COPD, diabetes or erectile dysfunction, he said.