A recent review published in Clinics in Liver Disease sheds light on cholestatic pruritus — a debilitating itch that burdens many people living with primary biliary cholangitis (PBC).
The itch affects up to 40% of people with chronic liver disease and as many as 81% of those with PBC. Far from a minor annoyance, it can disrupt sleep, drain energy and take a heavy toll on mood, daily functioning and social life. Yet it has long been hard to treat, in part because it does not respond to the drugs that calm ordinary allergic itch.
Read more about PBC signs and symptoms
Antihistamines, the standard allergy medicines that ease itching from an allergic reaction, are not effective against cholestatic itch. The reason, the authors note, is that this itch does not depend on histamine but instead arises through different biological pathways; any relief patients do feel is thought to come from the drugs’ sedating effect rather than a true anti-itch action.
Some medicines developed for other conditions may help instead. Certain antidepressants called selective serotonin reuptake inhibitors (SSRIs), such as sertraline, appear to dampen how the brain perceives itch. Opioid antagonists such as naloxone and naltrexone — better known for treating opioid overdose and addiction — may help by blocking the body’s own opioid-like chemicals, which build up in liver disease and amplify itch signals.
For severe cases that resist medication, hospital-based blood-filtering treatments, including plasmapheresis and a form of albumin dialysis called molecular absorbents recirculating system (MARS), can strip itch-causing substances from the bloodstream, though the relief is often temporary.
Bile acids, which accumulate when bile flow is impaired (called cholestasis), have long been suspected culprits for itching. Their levels in the skin mirror those in the blood, but neither reliably predicts how severe a person’s itch will be. Even so, treatments that lower bile acids do help, pointing to a real, if complex, role.
Researchers are also focusing on interleukin-31 (IL-31), an itch-signaling protein. Interestingly, drugs that activate the farnesoid X receptor (FXR), such as obeticholic acid, can raise IL-31 and often cause itching as a side effect. Obeticholic acid is second-line therapy for PBC that was withdrawn from U.S. market last year.
Much of the recent progress comes from two newer classes of drugs. Peroxisome proliferator-activated receptor (PPAR) agonists — including seladelpar, elafibranor and bezafibrate — help regulate how the body handles bile acids and calm inflammation, and seladelpar has also been shown to lower IL-31.
Ileal bile acid transporter (IBAT) inhibitors take a different approach, blocking a protein that recycles bile acids in the gut. One of them, linerixibat, became the first therapy the U.S. Food and Drug Administration has approved specifically for PBC-related itch, in March 2026.
The authors said that success should not be measured just by lowering the itch score, but rather by breaking “the debilitating cycle of sleep deprivation, chronic fatigue, and depression, profoundly improving patients’ quality of life.”
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