We are at the forefront in the exploration of treatments for ascites, the condition characterized by the excessive accumulation of abdominal fluid. Ascites frequently occurs in cases of advanced liver cirrhosis, which can result from the progression of metabolic dysfunction-associated steatohepatitis (MASH), infection with Hepatitis B & C, alcoholism, and other factors. It's worth noting that ascites is the most common complication associated with advanced ("decompensated") liver cirrhosis, and its complications can pose life-threatening risks.
Presently, clinical outcomes for this condition do not generally offer a favorable outlook. Some individuals diagnosed with cirrhosis and ascites may find a promising option in the form of a liver transplant.
Targeting Ascites
In our pursuit of a breakthrough, we are taking a fresh and comprehensive approach to understanding the biology and physiology underlying ascites. Our strategy involves synergizing existing technologies with innovative applications to craft a potential remedy for this challenging condition. This endeavor represents a critical milestone in our commitment to addressing the pressing medical needs of patients affected by ascites, offering them new hope for improved quality of life and better outcomes.
Chronic Liver Disease
Chronic liver disease (CLD), including cirrhosis, is responsible for the death of 42,000 Americans each year. As a population, people diagnosed with both liver cirrhosis and ascites are hospitalized 116,000 times each year, incurring an estimated $5 billion in annual treatment costs.
There are 3 major causes of liver cirrhosis. The fastest-growing cause of liver cirrhosis is metabolic dysfunction-associated steatohepatitis (MASH), which can develop from fatty-liver disease due to obesity, and whose diagnosis has reached epidemic rates. MASH progresses to fibrosis and cirrhosis is now the leading reason for liver transplants. Alcoholism accounts for about 25% of all causes of cirrhosis and is rising. Hepatitis C is another leading cause of liver cirrhosis and ascites. Although the new antiviral therapies will eventually reduce the number of people affected by viral hepatitis, these life-saving therapies have not arrived in time for many people whose livers have already been irreversibly damaged by Hepatitis C.
It may take decades for damage to accumulate and for cirrhosis to destroy the liver. At first, the liver may be in a “compensated” state, meaning that the liver is still cleansing the blood and performing other important functions. Once the liver reaches the “decompensation” stage it is no longer functional, and ascites and other deadly complications start to occur.
How Ascites Develops
In advanced liver cirrhosis, the liver becomes “clogged,” and blood pools in the region below the liver, called the splanchnic bed, because it can’t flow through the liver. This increases pressure in the portal vein, which supplies blood to the liver.
With blood pooling below the liver, the blood volume in the arteries decreases and the person with cirrhosis experiences “low effective blood volume.” In an effort to correct this situation, the brain sends signals via the renin-angiotensin-aldosterone system (“RAAS”) to the kidneys to retain extreme amounts of water and salt to attempt to reflexively increase the blood volume in the arteries. The excess liquid weeps from the lymphatic system and collects in the abdomen – which is when ascites appears.
We are investigating BIV-201 for the treatment of ascites. BIV-201 is a novel, continuous infusion formulation of terlipressin delivered via a small, portable pump that patients can wear while engaging in typical tasks and activities at home.
