Primary biliary cholangitis (PBC)—previously called primary biliary cirrhosis—is a chronic autoimmune disorder of the liver in which an individual’s bile ducts become injured, inflamed and then slowly destroyed.
Bile that is produced in the liver travels through these ducts to the small intestine, where the digestion of fat and fat-soluble vitamins occurs. Destruction of these ducts causes the buildup of bile in the liver, which can lead to inflammation and scarring (fibrosis).
Why does cirrhosis occur?
Ultimately, such bile duct destruction can result in cirrhosis, in which severe scarring of the liver occurs. The scar tissue replaces healthy liver tissue, and liver function becomes more and more impaired.
Every time a person’s liver becomes injured, it tries to repair itself, which causes more scar tissue to develop. When cirrhosis worsens, additional scar tissue continues to form, which makes it challenging for the liver to do its job. Advanced cirrhosis eventually can develop, which is a life-threatening condition.
How common is PBC?
About 25% of individuals with PBC are women who are younger than 40 years of age, and approximately 10% of patients are men. PBC usually manifests during middle age, with individuals between 45 and 65 years of age the population most affected.
It is estimated that around 65 of every 100,000 women in the United States have PBC.
What are the symptoms associated with PBC?
In the early stages of PBC, patients often do not have any symptoms. Initially, the most common symptoms of disease are fatigue and pruritus (itchy skin). Other possible symptoms include dry mouth/eyes, brain fog, joint pain/stiffness, darkening of the skin, and abdominal pain.
As the disease progresses, symptoms of cirrhosis can develop, including jaundice (yellowing of the skin), ascites (enlarged abdomen due to fluid retention), edema (swelling of legs/feet), and varices (internal bleeding in upper stomach and esophagus).
What causes brain fog in patients with PBC?
Cognitive dysfunction is described by patients as “brain fog.” It involves difficulty concentrating and processing information, along with short-term memory lapses. Approximately one-third of individuals with PBC experience symptoms of fatigue and substantial cognitive deficits. Patients who experience brain fog report that it is associated with fatigue and that it interferes with their daily lives.
In fact, fatigue is associated with memory changes, sleep disturbances, difficulty concentrating, mood alterations, and impaired physical activity. Experiencing fatigue can limit an individual’s ability to work and perform activities of daily living. Fatigue is known to affect a person’s mood and to have a strong negative impact on quality of life.
What treatments are available for PBC?
Treatment in patients with PBC is aimed at easing symptoms and slowing disease progression. Although ursodeoxycholic acid (UDCA) is considered the first-line treatment, the use of combination therapies recently has gained interest.
In patients who do not have a sufficient response to UDCA, obeticholic acid (OCA) can be added. OCA has been shown to reverse cognitive impairment in a rodent model of bile duct ligation–induced PBC. Other possible treatments include budesonide, peroxisome proliferator-activated receptor (PPAR) agonists, and the NOX-1,4 inhibitor setanaxib.
None of these treatments, however, appear to have an impact on behavioral issues among individuals with PBC.
How can brain fog and memory issues be treated?
Currently, no pharmacologic therapy (medication) has been approved to treat cognitive symptoms and fatigue in patients with PBC, with clinicians relying solely on supportive therapies.
The use of nonpharmacologic interventions such as cognitive remediation (rehabilitation) and exercise represent possible targets for the treatment of PBC. Cognitive remediation therapy may help to improve attention, memory, and cognitive function.
The GABAA (gamma-aminobutyric acid type A) receptor-modulating steroid antagonist golexanolone is being evaluated in a phase 2a study as a treatment for hepatic encephalopathy (HE). HE is described as a temporary nervous system disorder that is exacerbated by severe liver disease. Toxic substances can accumulate in the blood of individuals whose liver does not function properly. These toxins can then travel to the brain and impact brain function.
