PH and Liver Disease

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What is liver disease?

To understand liver disease, it is first essential to know what the liver does. The liver is the largest glandular organ in the body, and it has many jobs. It provides a substance that breaks down fats, produces several important compounds, stores certain vitamins, makes specific amino acids, converts glucose to glycogen, and makes sure there are certain levels of glucose in the blood. Most importantly for this discussion, however, the liver filters the blood and removes harmful substances from it.

Because it has so many jobs to do, the liver is an extremely important organ in keeping the body healthy. Therefore, if the liver becomes damaged or diseased, it creates problems throughout the body. Liver disease can take the form of cirrhosis (damage and scarring of the liver tissues that results in blocked blood flow and impaired liver function), or obstruction of blood flow to the liver without cirrhosis.

How does liver disease relate to pulmonary hypertension?

Liver disease can cause what is known as “portal hypertension,” meaning increased blood pressure in the veins that enter the liver. This increased pressure causes blood to bypass the liver; as a result, the blood is not subject to the liver’s work, which includes the removal or detoxification of chemicals and poisons in the body.

As a result, the blood vessels of the lung are exposed to possible toxic substances and this can damage the small arteries of the lungs, causing pulmonary arterial hypertension (PAH).

What is POPH?

Portopulmonary hypertension, or POPH, is a type of PAH that occurs as a result of advanced liver disease. This disease has the same characteristic symptoms as those found in cases of PAH that are not associated with liver disease.

Those characteristic symptoms of POPH include blood clots and other changes in the blood vessels of the lung. Symptoms the patient may notice are similar to those associated with classic PH, and include shortness of breath and limited ability to tolerate exercise.

Why does POPH develop?

The reason that POPH develops is unclear, but research has given us some clues. It is known that patients with POPH have a deficiency of prostacyclin (a substance that causes the blood vessels to relax), and an excess of endothelin I (an inflammatory mediator that causes the blood vessels to constrict, and also causes the inner and middle layers of the arteries of the lung to grow).

In addition, it appears that women and those with autoimmune-related cirrhosis may be predisposed to POPH. Most patients diagnosed with POPH are adults; few are children.

What makes POPH so serious?

In addition to the fact that POPH is a complication of liver disease (which is in itself very serious), POPH is a serious risk factor if a patient is being considered for a liver transplant. The risk of complications and death increase in a transplant patient with moderate or severe POPH.

How is POPH diagnosed?

A specialist can diagnose POPH by identifying portal hypertension (high pressure in the veins of the liver), in conjunction with the usual signs of PAH. Patients who are being screened to be liver transplant candidates are given an echocardiogram as part of established practice guidelines.

If the echocardiogram shows that the pressure in the right side of the heart is abnormally high, that patient will need to have another test, known as a right heart catheterization, to rule out POPH.

Any patient with chronic liver disease and shortness of breath (even if he or she is not considering a transplant) should discuss with a specialist the possibility of having echocardiography to be screened for PH.

How is POPH treated?

Treatment of patients with POPH is an area that is still being studied. Because patients with POPH have not been included in many of the regular PAH drug studies, our knowledge is limited in terms of which drugs are most beneficial in caring for POPH patients.

However, there is hope on the horizon. Small studies done in the U.S. with epoprostenol have been encouraging. In both Europe and the U.S., improvement in POPH patients has also been seen in small drug studies with bosentan, ambrisentan, or sildenafil.

Can patients with POPH be candidates for a liver transplant?

There is not yet an easy answer to this question, again because studies are so limited. The outcome for patients with POPH when liver transplant is attempted continues to be unpredictable. If the pressure is high in the lungs during transplant, mortality during and after surgery is more likely.

However, limited but encouraging data suggests that patients who respond to 24-hour continuous intravenous epoprostenol, treprostinil, oral bosentan or sildenafil and who then undergo liver transplantation have excellent survival and in some cases complete resolution of POPH.

In all cases, the sooner a patient is tested, the sooner problems like POPH can be ruled out or addressed, generally leading to a better outcome for the patient.