Learn The BasicsThere is no cure for primary biliary cholangitis (PBC), but several therapeutic options are available. The goal of these therapies is to delay the progression of the disease. Others are currently being investigated in clinical trials, and if the trials produce positive results, they may eventually be available to patients.
Ursodeoxycholic acid (UDCA)
The main treatment for PBC is ursodeoxycholic acid (UDCA), also known as ursodiol, which is a naturally occurring secondary bile acid.
UDCA was originally approved by the FDA in 1987 to treat gallstones, but it was approved as a treatment for PBC in 1996.
It works by replacing the more toxic bile acids in the bile acid pool, thereby reducing their proportion. This way, liver cells and cells lining the bile ducts are protected.
Research has shown that it also helps preserve the structure of liver cells and stimulates biological pathways against programmed cell death. It can also reduce oxidative stress in the liver.
The side effects of UDCA include weight gain, nausea, diarrhea and hair thinning.
UDCA is sold under the brand names Reltone, Actigall or Urso.
Obeticholic acid (OCA)
OCA is a bile acid analog used to treat patients with PBC who cannot take UDCA or in combination with UDCA if the treatment is not working well enough. It was approved by the FDA in 2016.
OCA works by activating the farnesoid-X receptor (FRX), which regulates bile acid synthesis and transport.
When it binds to FRX, it reduces the synthesis of bile acids as well as inflammation and the resulting liver scarring. It also increases bile flow, thereby reducing the exposure of liver cells to toxic bile acids that damage them.
One of the main side effects of OCA is itching. It is sold under the brand name Ocaliva.
Budesonide
Budesonide is a corticosteroid that works by decreasing inflammation. It may be beneficial in combination with UDCA for the treatment of PBC, but more research is needed before it can be recommended in the clinic.
Budenoside is also associated with serious side effects such as worsening osteoporosis, which is already a problem in patients with PBC.
Fibrates
Fibrates are drugs that reduce the levels of a type of fat in the blood, called triglycerides. They have been used to lower cholesterol for many years and can also be used off-label to treat patients with PBC. Off-label means that a drug is used for a disease that is different from the one for which it was originally approved.
Fibrates work by binding to a protein called peroxisome proliferator-activated receptor (PPAR) and are protective against bile toxicity because they block the production of bile acid and stimulate the excretion of phospholipids.
American and European guidelines suggest that fibrates should be evaluated in patients with PBC in whom UDCA does not work well. However, they should not be used in patients with decompensated liver disease or symptomatic cirrhosis, as they are toxic to the liver.
Novel agents
There are other non-fibrate molecules that bind to PPAR and reduce the production of bile acids and control their transport and metabolism. These include seladelpar and elafibranor, which are currently being tested in late-stage clinical trials and have potential as future PBC therapies.
