Portal hypertension and why it’s important

Posted on 22-02-2016 , by: Dr. Peter Traber , in , 0 Comments

By Peter G. Traber, M.D. on February 22, 2016

Everyone has had the experience of having their blood pressure taken and knows the importance of a normal reading for good health. But most people have never heard of liver blood pressure. In fact, high liver blood pressure, called portal hypertension, is the primary reason for complications and death in patients with advanced chronic liver disease, called cirrhosis.

The liver has a dual blood supply, which is different than most parts of the body. For example the kidney, intestines, muscles and many other tissues have a single blood supply that comes directly through arteries via the heart. The liver has two blood supplies — one directly from an artery (similar to other tissues), and a second blood flow from the portal vein. The greater proportion of blood comes from the portal vein, which drains the blood from the abdominal organs (stomach, small and large intestine, pancreas, and spleen).

Portal blood brings nutrients and hormones from the gastrointestinal tract which are important for liver function and homeostasis of many bodily functions. After arterial and portal blood mixes and flows through the liver, it returns to the heart via the main vein in the body.

Liver disease has a profound effect on this blood flow. All chronic liver disease leads to scar formation, or fibrosis. Whether the disease is due to a virus, alcohol, or fat, this scar tissue accumulates in the liver, with the most advanced stage called cirrhosis. The fibrotic tissue of cirrhosis distorts the liver architecture, impeding liver blood flow and, as a result, the blood pressure in the portal vein increases — this is called portal hypertension.

portal hypertension

The figure shows what happens in portal hypertension. The increased pressure causes a certain type of vein dilations (similar to varicose veins or hemorrhoids), the most important of which are called esophageal varices. These dilated veins in the esophagus can burst and cause catastrophic bleeding. Another result of increased pressure is the build-up of fluid in the abdomen outside of the organs, called ascites, which is uncomfortable and can become infected. The increased pressure also results in additional vessels opening up, allowing blood to bypass the liver and enter directly into systemic circulation. Toxins that are normally removed by the liver gain direct access to the rest of the body and the brain, causing mental problems such as lethargy, confusion, and, in the worst cases, coma.

Portal hypertension does not occur with early stages of fibrosis but only when cirrhosis develops. In cirrhotic patients, the level of the portal pressure is directly related to the rate of cirrhotic complications and mortality. Additionally, if the portal pressure is decreased, the outcomes of patients are improved. This makes the portal pressure a potential surrogate for outcomes in clinical trials. If a drug therapy reduces portal pressure, it portends a better prognosis for the patient.

Measurement of portal pressure is not as simple as measuring systemic blood pressure. In fact, there is no direct way to measure portal pressure in clinical medicine. However, there is a minimally invasive radiology procedure that gives a very good estimate of portal pressure, called hepatic venous pressure gradient (HVPG). Rather than describe this technique, watch a short video of the procedure.

HVPG is the primary endpoint in our NASH-CX clinical trial, in which patients with cirrhosis are being treated with our galectin-3 inhibitor GR-MD-02 (see details of trial here). The goal of this trial is to reduce fibrosis in the liver, which will reduce the resistance to blood flow through the liver and, as a result, will reduce portal pressure and improve patient outcomes. It is important that we are also doing other tests for liver fibrosis and function, including liver biopsy (more here), FibroScan (more here), and the methacetin breath test (more here).

Measurement of HVPG to assess portal hypertension is a vital tool in evaluating potential therapies for liver cirrhosis. HVPG has been shown to be directly related to patient outcomes, making it a potential surrogate for drug registration trials.

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