Liver cirrhosis due to NASH, alcoholic liver disease and/or hepatitis is the 12th leading cause of death due to disease in the US, killing an estimated 27,000 people annually, and incurring treatment costs estimated at $4 billion annually. Ascites is liver cirrhosis’s most common complication and involves excessive accumulation of fluid in the abdomen, which can become life-threatening in patients with advanced liver cirrhosis. Patients with ascites suffer a miserable quality of life and frequent infections, as well as other complications requiring hospitalization that contribute to their decline.


Liver cirrhosis occurs when tissues inside the liver become damaged (“fibrotic”), which may be due to NASH (non-alcoholic steatohepatitis), alcoholism, hepatitis, or other causes. As the internal damage accumulates, the liver begins to “clog up” which impedes blood flow and its ability to clean and purify the blood. About 1 million Americans are afflicted with liver cirrhosis.

This is an illustration of the progression of a healthy liver to liver cirrhosis:


Once liver damage becomes very substantial, which may take up to 10 years or more, ascites and/or other serious complications may occur. Ascites is the most common complication, involving kidney dysfunction and the accumulation of substantial amounts of fluid in the abdominal cavity. This causes much patient suffering and sometimes leads to malnutrition. Ascites often causes other life-threatening complications such as infection, sepsis, and circulatory dysfunction.


With no medications approved by the FDA specifically to treat ascites, the prognosis for these patients is very poor. Certain drugs which have been approved for other medical conditions (such as diuretics) combined with a salt-restricted diet usually provide symptomatic relief in the initial stages of the disease. But as the ascites worsens their efficacy often diminishes. BioVie is working on a solution to address this critical unmet medical need.

Most experts agree that ascites develops through a sequence of events illustrated by this diagram:


High blood pressure in the vein that supplies blood to the liver, called “portal hypertension,” occurs as increasing liver damage (fibrosis) impedes blood flow through the liver. This causes vasodilation and blood pooling in the central or “splanchnic” region of the body and low blood volume in the arteries. The decrease in effective blood volume activates a signaling pathway (“neurohormonal systems”) which tells the kidneys to retain large amounts of salt and water in an effort to increase blood volume. Ultimately the retention of excess sodium and water leads to the formation of ascites as these substances “weep” from the liver and lymph system and collect in the patient’s abdomen.
BIV201 is being developed by BioVie with the goal of alleviating the portal hypertension and correcting splanchnic vasodilation, thereby increasing effective blood volume and reducing the signals to the kidneys to retain excess salt and water.