A Research Guide for
PBC

• Alkaline phosphatase (ALP) — The single most important number in PBC. ALP comes from injured bile-duct cells; it tracks both disease activity and treatment response.
• GGT (gamma-glutamyl transferase) — Confirms that an elevated ALP is coming from the liver rather than from bone.
• Bilirubin — Reflects the overall ability of the liver to clear bile; an early bilirubin rise is one of the most important warning signs in PBC.
• Albumin and INR — Markers of overall liver synthetic function; usually normal early in PBC.
• ALT and AST — The “liver enzymes” that get a lot of attention in other liver diseases; in PBC they are usually only mildly elevated.
• AMA (anti-mitochondrial antibody) — Positive in ~95% of PBC patients. AMA can be present years before any liver test changes.
• ANA (anti-nuclear antibody) and anti-sp100/anti-gp210 — Sometimes positive; anti-gp210 specifically is associated with more aggressive disease.
• Immunoglobulin M (IgM) — Often elevated in PBC, sometimes strikingly so.

An ultrasound of the liver is part of every initial evaluation. It is mainly to rule out other causes of an elevated ALP (such as gallstones or a blocked bile duct).

FibroScan (transient elastography) is a painless, non-invasive way to measure liver stiffness, which correlates with how much scarring has developed. It is repeated periodically — usually every 1–2 years — to track whether scarring is stable or progressing. A FibroScan value above 9–10 kPa generally suggests significant fibrosis; above 17 kPa suggests cirrhosis.

MRI/MRCP is sometimes added when the diagnosis is uncertain or to evaluate for primary sclerosing cholangitis (PSC), a different cholestatic disease that can look similar at first.

Most people with classic PBC (positive AMA, elevated ALP, no other explanation) do not need a liver biopsy. A biopsy is most useful when:

• The AMA is negative (so-called AMA-negative PBC, which is more common in Japan, accounting for up to 15–20% of cases there) and the diagnosis isn’t clear from blood tests
• There is suspicion of overlap with autoimmune hepatitis (PBC-AIH overlap), which changes treatment
• Another liver condition is suspected at the same time (e.g., fatty liver disease, drug-induced injury)
• Disease behaves unusually — for example, lab values that don’t fit the typical PBC pattern

After you have been on UDCA for a year, your hepatologist can use validated calculators to estimate your long-term risk:

• GLOBE score — Developed from an international study across 8 countries; estimates 5-, 10-, and 15-year transplant-free survival.
• UK-PBC score — Developed from the UK national PBC registry of more than 8,000 patients; estimates risk of liver transplant or death at 5, 10, and 15 years.

Both use combinations of ALP, bilirubin, albumin, platelets, AST/ALT, and age. They are most useful for deciding whether to add a second-line medication and how often to monitor.

• What is my current ALP, bilirubin, albumin, platelet count, and FibroScan reading? Can I have a copy?
• Is my AMA positive? If not, what other tests are you using to confirm PBC?
• Do I need a liver biopsy, and if so, why?
• What stage of PBC do you think I have — early, moderate, or with cirrhosis?
• What is my GLOBE score and UK-PBC score? Are you using them to guide my treatment?
• Do I have signs of any overlap with autoimmune hepatitis?
• Should I be screened for celiac disease, thyroid disease, or Sjögren’s syndrome?
• How often will you re-check my labs and FibroScan?
• Can I be referred to a hepatologist if I am not already seeing one?

• Dose: 13–15 mg per kg of body weight per day. For a 70 kg (155 lb) person, that’s about 1000 mg/day; for a 90 kg (198 lb) person, about 1250–1350 mg/day.
• Dosing schedule: Usually split into 2–4 doses with meals, though many people now take the full daily dose once daily at bedtime, which works just as well and improves adherence.
• With food: Recommended; food helps absorption.
• Timing relative to cholestyramine: If you also take cholestyramine for itching, UDCA needs to be taken at least 1 hour before or 4 hours after.
• Forever: UDCA is a lifelong therapy. Stopping it leads to lab values worsening within weeks to months.

UDCA is one of the best-tolerated medications in liver disease. The most common side effect is weight gain of 2–5 pounds in the first year (the mechanism isn’t fully understood). Some people get mild diarrhea, hair thinning, or bloating in the first few weeks, which usually settles. Serious side effects are very rare.

After about a year on UDCA, your hepatologist checks whether you are an “adequate responder.” Several criteria are used:

• Paris II criteria (commonly used for early disease) — ALP ≤ 1.5 × upper limit of normal (ULN), AST ≤ 1.5 × ULN, and bilirubin ≤ 1 mg/dL.
• Toronto criteria — ALP ≤ 1.67 × ULN.
• Barcelona criteria — A drop in ALP of more than 40% from baseline, or normalization.

About 60–70% of people will meet criteria for adequate response at 12 months. If you don’t, that does not mean UDCA has failed — it means you likely need additional treatment on top of UDCA, not instead of it.

UDCA intolerance is rare but real (probably less than 3% of patients). If you genuinely cannot tolerate UDCA, both elafibranor and seladelpar are FDA-approved for use as monotherapy in UDCA-intolerant patients. Make sure your hepatologist confirms true intolerance — not just early gastrointestinal side effects that often pass with dose adjustment or switching brands.

• Am I on the correct weight-based dose of UDCA (13–15 mg/kg/day)?
• When will you check whether I have responded to UDCA?
• Which response criteria are you using (Paris II, Toronto, Barcelona, GLOBE)?
• If I am not a full responder, what is your plan — elafibranor, seladelpar, fibrate add-on, or referral?
• Should I get my UDCA from a particular pharmacy or in a particular formulation?
• Are there any drugs I should avoid while on UDCA? (Cholestyramine timing, certain antacids.)
• Is there any reason to consider lowering or stopping UDCA (e.g., decompensated cirrhosis — though most patients continue it)?

Elafibranor is a once-daily 80 mg oral tablet that activates two related receptors called PPAR-alpha and PPAR-delta. These receptors regulate bile-acid production, inflammation, and fibrosis in the liver. By reducing how much bile acid your liver makes and increasing how much it exports, elafibranor lowers the buildup of toxic bile acids that drives PBC.

In the pivotal Phase 3 ELATIVE trial, 51% of patients on elafibranor plus UDCA met the composite biochemical response endpoint at 52 weeks, compared with only 4% on placebo plus UDCA — a 47-percentage-point absolute difference. Longer-term follow-up out to three years has shown continued improvement in liver labs and meaningful improvements in fatigue and itching.

• Most common: weight gain, abdominal pain, diarrhea, nausea, muscle aches
• Less common but watched for: muscle injury (CK monitoring), gallstones, fractures (PPAR effects on bone)
• Not recommended in decompensated cirrhosis (Child-Pugh B or C) per FDA label
• Cost: very high; specialty pharmacy access and prior authorization are usually required. Most commercial plans cover it; Medicare coverage varies. Ipsen patient-assistance programs are available.

Seladelpar is a once-daily 10 mg oral capsule that selectively activates the PPAR-delta receptor. It improves bile-acid handling and has anti-inflammatory and anti-itch effects. It is the first PBC drug to demonstrate a statistically significant improvement in both liver biochemistry and itching in its pivotal trial.

In the pivotal Phase 3 RESPONSE trial, 62% of patients on seladelpar plus UDCA met the composite biochemical response endpoint at 12 months, compared with 20% on placebo plus UDCA. ALP normalization (a clear marker of how completely the disease is being controlled) was achieved in 25% of seladelpar-treated patients versus 0% on placebo.

• Most common: headache, abdominal pain, nausea, abdominal distension, dizziness
• Generally well tolerated in trials; comparable safety profile to placebo
• Not recommended in decompensated cirrhosis per FDA label
• Approved as accelerated approval — final approval will depend on the ongoing AFFIRM confirmatory trial
• U.S. list price approximately $12,606 per 30-day supply; Gilead patient-assistance programs are available

Fibrates are inexpensive, decades-old cholesterol drugs that happen to be PPAR-alpha activators. They have been used off-label in PBC for over twenty years in Japan and Europe.

• Bezafibrate — The BEZURSO trial (France, 100 patients, NEJM 2018) showed that adding bezafibrate to UDCA produced complete biochemical response in 31% versus 0% on placebo. Bezafibrate is not available in the U.S. but is widely used in Europe, Asia, and Canada.
• Fenofibrate — Available in the U.S.; evidence is mostly from retrospective and observational studies, but consistent with bezafibrate’s effects. Dosing is typically 145–200 mg daily.

Fibrates are usually avoided in advanced cirrhosis because of safety concerns. Side effects include muscle aches, mild kidney effects, and gallstones.

1. Skin care basics — cool baths, mild fragrance-free moisturizer, cotton clothing, keeping fingernails short, room temperature on the cool side at night.
2. Cholestyramine (Questran) — A bile-acid binder taken as a powder. First-line in guidelines. Must be taken at least 1 hour before or 4 hours after UDCA and other medications. Common side effects: bloating, constipation. Many people find it unpalatable.
3. Rifampicin (rifampin) — An antibiotic with strong anti-itch effects. Starts at 150 mg/day, can go up to 600 mg/day. Requires baseline and follow-up liver tests because of rare drug-induced liver injury. Will turn body fluids orange.
4. Opioid antagonists (naltrexone, nalmefene) — Block itch-signaling pathways in the brain. Can cause a temporary “opioid-withdrawal-like” reaction in the first few days; usually started at very low dose.
5. Sertraline — A common antidepressant that has anti-itch effects in cholestasis at 75–100 mg/day.
6. Seladelpar (Livdelzi) — Provides a meaningful reduction in itch in the pivotal RESPONSE trial, and is increasingly being chosen specifically for patients whose itching is a dominant problem.
7. Linerixibat (Lynavoy) — FDA approved March 2026 — The first drug ever approved specifically for cholestatic pruritus in PBC. An IBAT (ileal bile acid transporter) inhibitor that reduces the pool of bile acids driving the itch. Dose: 40 mg twice daily. The GLISTEN Phase 3 trial (115 centers, 19 countries) showed significant itch reduction starting at week 2 and sustained over 24 weeks, with improved sleep. This is a major breakthrough for the many PBC patients whose itching has been inadequately controlled.
8. Maralixibat — Another IBAT inhibitor approved for itching in different cholestatic diseases (Alagille syndrome, progressive familial intrahepatic cholestasis) but not yet in PBC.
9. Nasobiliary drainage or molecular adsorbent recirculating system (MARS) — For severe, refractory cases, performed at major liver centers.

Fatigue affects roughly half to three-quarters of people with PBC and is the symptom most likely to interfere with work and daily life. Frustratingly, no pill is approved specifically for PBC-related fatigue. Things that genuinely help most people:

• Screening and treating contributors: thyroid disease, sleep apnea, depression, vitamin D deficiency, anemia
• Pacing — spreading activity across the day instead of pushing through
• Regular gentle exercise (counterintuitive but consistently helpful)
• Sleep hygiene and treating itching that disrupts sleep
• Cognitive behavioral therapy for fatigue, where available

Some patients report fatigue improves on elafibranor (recent ELATIVE follow-up data showed a statistically significant fatigue benefit at 52 weeks). Modafinil has been tried with mixed results; it is not part of standard guidelines for PBC fatigue.

For many people with PBC, the standard of care is now very good. But clinical trials remain worth considering if: you have ongoing inadequate response, you have refractory itching, you have advanced fibrosis, or you simply want access to investigational therapies.

Active trial categories to ask about:

• Linerixibat (Lynavoy) long-term extension studies — GLISTEN extension (NCT04950127)
• Setanaxib (a NOX1/4 inhibitor) for liver fibrosis in PBC — TRANSFORM Phase 2b (NCT05014672); Phase 3 anticipated
• CNP-104 — A novel tolerance-inducing nanoparticle therapy targeting the immune cause of PBC; FDA Orphan Drug and Fast Track designations — Phase 2b expected 2025
• Seladelpar confirmatory trials: AFFIRM (NCT06051617) in compensated cirrhosis; ASSURE long-term extension (NCT03301506)
• Elafibranor confirmatory trials: ELFIDENCE (NCT06016842) in compensated cirrhosis; ELFINITY long-term outcomes
• Pemafibrate (selective PPAR-alpha modulator) — Phase 2 (NCT06247735); estimated completion June 2026
• Saroglitazar (Zydus; a PPAR-alpha/gamma agonist) — the seamless Phase 2b/3 EPICS-III trial (NCT05133336) in patients with an inadequate response to UDCA has completed, with topline results reported at the EASL Congress 2026; the manufacturer described a higher biochemical response than placebo. The U.S. FDA granted saroglitazar Priority Review for PBC in May 2026, with a decision expected in late 2026. It remains investigational and is not yet FDA-approved.

ClinicalTrials.gov is the best starting place. The University of Utah and Intermountain Health both participate in selected hepatology trials.

• Am I an adequate or inadequate responder to UDCA based on the criteria you use?
• Should I be on a second-line drug — elafibranor, seladelpar, or a fibrate — and if so, which one and why?
• If I was previously on Ocaliva, what is your transition plan?
• How much do my insurance and copay assistance programs cover for elafibranor or seladelpar?
• How will you measure whether the second-line drug is working?
• What stepwise plan do you have for my itching, and how high are we willing to go on the ladder?
• Have you screened me for sleep apnea, thyroid disease, and depression as contributors to my fatigue?
• Am I a candidate for any current clinical trial?

Cholestatic liver disease accelerates bone loss. Osteoporosis is two to four times more common in PBC than in age-matched women without PBC. Every patient should have:

• A baseline DXA bone density scan at diagnosis, repeated every 2–3 years (more often if low)
• Vitamin D level checked yearly; supplementation as needed
• Adequate calcium (1000–1200 mg/day, food preferred over supplements)
• Weight-bearing exercise
• Bisphosphonate or other osteoporosis treatment if DXA shows osteoporosis, after talking with a hepatologist about which to choose (oral bisphosphonates need caution in advanced PBC)

Many people with PBC have very high cholesterol numbers because of disrupted bile flow. Counterintuitively, this elevated cholesterol does not appear to translate into a higher heart-attack rate in PBC, except in patients who have the usual risk factors (smoking, diabetes, family history, hypertension).

If your hepatologist recommends a statin, it is generally safe in PBC (despite older worries) and may even have a small additional benefit. Don’t avoid a statin just because you have PBC.

When bile flow is reduced, absorption of fat-soluble vitamins drops. Vitamin D deficiency is the most common; vitamin K deficiency (a bleeding risk) shows up later when cholestasis is severe. Annual vitamin D testing is standard; broader fat-soluble vitamin panels are reasonable in jaundiced or cirrhotic patients.

Two cancer-screening points are PBC-specific:

• Hepatocellular carcinoma (HCC): Patients with cirrhosis should have abdominal ultrasound every 6 months (sometimes alternated with MRI). Men with PBC, and patients who don’t respond to UDCA, are at higher relative risk.
• Routine age-appropriate cancer screenings (breast, colon, cervical, lung) follow the same rules as the general population. PBC doesn’t increase these.

• Alcohol: Best to avoid, or keep to very minimal amounts (no more than one drink occasionally if non-cirrhotic and your hepatologist agrees). Strictly none if cirrhotic.
• Diet: No specific PBC diet. A Mediterranean-style pattern is sensible. Limit ultra-processed foods.
• Smoking: Smoking is associated with worse PBC outcomes. Quit if you can.
• Exercise: Yes — gentle, regular, sustainable. It helps fatigue, bones, mood, and cardiovascular health.
• Vaccinations: Stay current on hepatitis A and B (if non-immune), influenza, pneumococcal, RSV (per age guidelines), and COVID-19 vaccines.

Pregnancy is usually safe in non-cirrhotic PBC. UDCA is considered safe in pregnancy and breastfeeding and is generally continued. Elafibranor and seladelpar are not recommended in pregnancy or breastfeeding; family planning conversations should happen before starting them. Itching often worsens during the third trimester and should be managed proactively.

Modern PBC care has dramatically reduced the need for transplant, but it remains the right answer for a minority of patients with:

• Decompensated cirrhosis (significant ascites, variceal bleeding, hepatic encephalopathy)
• A MELD score that indicates high short-term mortality
• Refractory itching that is destroying quality of life despite all medical options (this is one of the few quality-of-life indications for transplant)
• Liver cancer (HCC) meeting transplant criteria

Outcomes after transplant for PBC are excellent — 5-year survival is approximately 80–85%, among the best of any indication. PBC recurs in the transplanted liver in roughly 25–35% of patients over time, but is usually mild and managed with continued UDCA.

• New jaundice (yellowing of skin or eyes) that wasn’t there before
• Confusion, drowsiness, or trouble concentrating that’s out of character (possible hepatic encephalopathy)
• Vomiting blood, or stools that are black and tarry (possible variceal bleed — ER immediately)
• Sudden severe abdominal pain or rapid abdominal swelling
• Severe new itching that is preventing sleep
• Any new bruising or bleeding without a clear cause
• Fever and right-upper-quadrant pain (possible cholangitis)

How you can help. Being a caregiver for someone with PBC is different from caregiving in acute illness — the disease is mostly slow and invisible, but it has real ups and downs. Practical ways to help:

• Adherence: UDCA must be taken every day, indefinitely. A pill organizer or phone reminder system, especially in the early months, makes a real difference.
• Sleep and itching: Cool bedrooms, breathable bedding, and protecting the bedroom as a low-stress zone help with nighttime pruritus. If your loved one is up scratching, that lost sleep is part of the disease.
• Fatigue: Believe them when they say they’re tired. PBC fatigue is real and not laziness. Help by taking over scheduling, errands, or driving on hard days, and resisting the urge to push them through it.
• Appointments: Going to hepatology appointments with them and taking notes is invaluable. Bring a written list of questions and current medications. Ask for a copy of every lab report.
• Watch for warning signs: New jaundice, confusion, GI bleeding, or worsening swelling should trigger a call to the hepatologist or an ER visit.
• Transplant evaluation: If your loved one is being evaluated for transplant, expect a multi-day workup involving cardiology, pulmonary, psychiatry, social work, and financial review. Being present for as much of it as possible is enormously supportive.
• Care for yourself: Chronic illness is a marathon. Schedule your own breaks, see your own doctor, lean on extended family. Local PBC Foundation chapters and the American Liver Foundation have caregiver-specific resources.

• University of Utah Health Hepatology — Cholestatic liver disease clinic at U of U Hospital and Huntsman Cancer Institute. UNOS Region 5 transplant center. Active in national hepatology trial networks. (Salt Lake City) — Main line: 801-581-2121 · Liver/GI clinic: 801-585-6387
• Intermountain Health Liver Disease Program — Regional hepatology coverage across Intermountain’s Salt Lake, Murray, and Provo facilities. (Multiple Utah locations) — Main line: 801-442-2000
• University of Utah Transplant Center — The transplant center serving Utah, Idaho, Wyoming, and parts of Nevada and Montana. Comprehensive pre- and post-transplant care. — Main line: 801-581-2121

Ask your primary care doctor for a hepatology referral if you don’t already have one — this is the single highest-impact step you can take after diagnosis.

• PBC Foundation (pbcfoundation.international) — The leading international PBC patient organization. Free helpline, regular webinars, advocacy.
• American Liver Foundation (liverfoundation.org) — Patient education, support groups (several Utah-area chapters), and financial-assistance resources.
• PBCers Organization (pbcers.org) — Active patient community with online forums and educational content.
• Global Liver Institute (globalliver.org) — Policy and advocacy on liver disease, including PBC-specific initiatives.

• ClinicalTrials.gov — Search “primary biliary cholangitis” with filters for recruiting status, location, and study phase.
• University of Utah Clinical Trials — healthcare.utah.edu/clinical-trials
• WHO International Clinical Trials Registry Platform (trialsearch.who.int) — For trials outside the U.S.

• Iqirvo (Ipsen) patient support program — Co-pay assistance and patient access services for commercially insured patients.
• Livdelzi (Gilead) patient support program — Co-pay assistance and free-drug programs for eligible patients.
• PAN Foundation (panfoundation.org) — Disease-specific grants for medication co-pays and out-of-pocket costs for PBC.
• HealthWell Foundation — Grants for cholestatic liver disease treatment costs.

The 2024 PPAR agonist approvals are still being absorbed by clinical practice. Realistically:

• Many general gastroenterologists are still in the learning curve on elafibranor and seladelpar; hepatology referral is increasingly important.
• Insurance prior authorization for both drugs can be slow; expect to involve specialty pharmacy and patient-assistance programs.
• Some patients on Ocaliva (obeticholic acid) have not been transitioned promptly to a successor drug after the September 2025 U.S. withdrawal — if that’s you, request a hepatology visit specifically to discuss transition.
• AMA-negative PBC is still under-diagnosed in the U.S.; liver biopsy is sometimes needed and shouldn’t be deferred.

Constructive next step: bring this guide (or specific sections) to your next appointment as a starting point for shared decision-making with your hepatologist.

• University of Utah Health Hepatology — Cholestatic liver disease clinic at U of U Hospital. UNOS Region 5 transplant center. Active in national hepatology trial networks including ELATIVE and RESPONSE extensions. (Salt Lake City) — Main line: 801-581-2121 · Liver/GI clinic: 801-585-6387
• Intermountain Health Liver Services — Regional hepatology coverage across Intermountain’s Salt Lake, Murray, and Provo facilities. Referral pathways for PBC patients who need second-line therapy evaluation. (Multiple Utah locations) — Main line: 801-442-2000

• Mayo Clinic Hepatology — Rochester, MN. One of the world’s leading PBC research centers; contributed to the development of the GLOBE score and multiple PBC trial networks. — Appointments: 507-284-2511
• UCSF Liver Center — San Francisco, CA. Major cholestatic liver disease program with active PBC clinical trials. — Appointments: 415-353-2318
• Mount Sinai Liver Diseases — New York, NY. Comprehensive hepatology with PBC specialty expertise and transplant program. — Appointments: 212-241-6500
• Yale Liver Center — New Haven, CT. Active PBC clinical trials program and liver transplant center. — Appointments: 203-785-4138

• George E. Wahlen VA Medical Center — GI/Hepatology (Salt Lake City) — Veterans with PBC can access hepatology evaluation, UDCA and second-line therapy management, and FibroScan through the VA system. Referral to university transplant centers when needed. — Main line: 801-582-1565
• VA National Hepatology Resource Centers — The VA operates specialized hepatology/liver programs at multiple facilities including VA Palo Alto, Minneapolis VA, and VA Portland. Ask your local VA primary care provider for a hepatology consult or inter-facility referral if specialized PBC care is not available at your home VA.

• Toronto Centre for Liver Disease (University Health Network) — Toronto, ON. Major Canadian PBC research and clinical program; one of the largest liver transplant programs in North America. Bezafibrate is available in Canada (unlike the U.S.) as a second-line option. — Appointments: 416-340-4800
• McGill University Health Centre — Hepatology — Montreal, QC. Active in PBC clinical research and bilingual care. — Main line: 514-934-1934
• University of British Columbia — BC Hepatitis Program / Liver Clinic — Vancouver, BC. Regional referral center for cholestatic liver disease in Western Canada. — Main line: 604-875-5171
• Canadian Liver Foundation — Patient advocacy and support resources for Canadian PBC patients. Connects patients with hepatology referrals across provinces.

• UK:
  • Newcastle upon Tyne Hospitals NHS Trust — Liver Unit — Newcastle, UK. One of the world’s leading PBC research programs; home to the UK-PBC Consortium and key investigators in PBC trial networks. — Main line: +44 191 233 6161
  • Queen Elizabeth Hospital Birmingham — Liver Unit — Birmingham, UK. Major hepatology center with active PBC clinical trials and transplant program. — Main line: +44 121 371 2000
  • UK PBC Foundation (pbcfoundation.org.uk) — The world’s leading PBC patient advocacy organization. Free nurse helpline, patient conferences, and the UK-PBC Research Programme that developed the UK-PBC risk score. Based in Edinburgh.
• Europe:
  • Hôpital Saint-Antoine — Hepatology — Paris, France. Home of the BEZURSO trial and Paris response criteria for PBC. — Main line: +33 1 49 28 20 00
  • Hannover Medical School — Hepatology — Hannover, Germany. Leading German center for autoimmune and cholestatic liver diseases. — Main line: +49 511 532 0
• Japan/Asia:
  • Teikyo University Hospital — Hepatology — Tokyo, Japan. Major center for PBC research including AMA-negative PBC and bezafibrate studies. — Main line: +81 3 3964 1211
  • Hiroshima University Hospital — Gastroenterology — Hiroshima, Japan. Leading center for cholestatic liver disease research in Japan. — Main line: +81 82 257 5555
• EASL PBC Guidelines Group — The European Association for the Study of the Liver publishes the international PBC clinical practice guidelines, most recently updated in 2024. EASL guidelines are widely followed outside the U.S.

• ALP (alkaline phosphatase) — a liver enzyme released by injured bile-duct cells; the single most important blood test for tracking PBC disease activity and treatment response.
• AMA (anti-mitochondrial antibody) — a highly specific blood antibody found in roughly 95% of PBC patients; its presence, combined with elevated ALP, is usually sufficient for diagnosis.
• Bezafibrate — a fibrate drug (PPAR-alpha agonist) used off-label as add-on therapy for PBC in Europe, Asia, and Canada. Not available in the U.S. The BEZURSO trial (NEJM 2018) demonstrated efficacy.
• Cholestyramine — a bile-acid-binding resin taken as a powder; the first-line treatment for PBC-related itching. Must be taken at least 1 hour before or 4 hours after UDCA and other medications.
• Cirrhosis — advanced scarring of the liver where normal tissue is replaced by scar tissue, impairing liver function. Most PBC patients diagnosed and treated early never develop cirrhosis.
• Elafibranor (Iqirvo) — an oral PPAR-alpha/delta agonist approved by the FDA in June 2024 for PBC patients who do not respond adequately to UDCA, or who are UDCA-intolerant. Taken as an 80 mg tablet once daily.
• Fenofibrate — a fibrate drug available in the U.S. and used off-label as add-on therapy in PBC. Evidence is mostly from observational studies but is consistent with bezafibrate results. Typical dose: 145–200 mg daily.
• Fibrate — a class of lipid-lowering drugs (bezafibrate, fenofibrate) that activate PPAR-alpha receptors. Used off-label in PBC as add-on therapy when UDCA alone is insufficient.
• FibroScan — a painless, non-invasive ultrasound-based device that measures liver stiffness to estimate the degree of fibrosis (scarring). Values above 9–10 kPa suggest significant fibrosis; above 17 kPa suggest cirrhosis.
• FXR agonist — a drug that activates the farnesoid X receptor, which regulates bile-acid production. Obeticholic acid (Ocaliva) was the only approved FXR agonist for PBC but was withdrawn from the U.S. market in 2025.

• GLOBE score — a validated calculator using ALP, bilirubin, albumin, platelet count, and age (measured after 12 months on UDCA) to estimate 5-, 10-, and 15-year transplant-free survival in PBC.
• Liver biopsy — a procedure in which a small sample of liver tissue is removed with a needle for microscopic examination. No longer required for routine PBC diagnosis but still used when AMA is negative or overlap syndromes are suspected.
• Obeticholic acid (OCA / Ocaliva) — an FXR agonist that was approved in 2016 for PBC as add-on to UDCA. Carried an FDA boxed warning about liver injury in advanced cirrhosis. Voluntarily withdrawn from the U.S. market in September 2025.
• Paris criteria — a set of biochemical thresholds (ALP, AST, bilirubin) measured after 12 months on UDCA to determine whether a patient is an adequate or inadequate responder. Paris II criteria are most commonly applied.
• PBC (primary biliary cholangitis) — a chronic autoimmune liver disease in which the immune system progressively destroys the small bile ducts inside the liver, leading to bile buildup, inflammation, and potentially cirrhosis. Formerly called primary biliary cirrhosis (name changed in 2015).
• Portal hypertension — abnormally high blood pressure in the portal vein (the large vein carrying blood from the intestines to the liver), caused by cirrhosis. Can lead to varices, ascites, and splenomegaly.
• PPAR agonist — a drug that activates peroxisome proliferator-activated receptors, which regulate bile-acid production, inflammation, and metabolism. Elafibranor (PPAR-alpha/delta) and seladelpar (PPAR-delta) are the two FDA-approved PPAR agonists for PBC.
• Pruritus — the medical term for itching; in PBC, caused by bile acids and other substances accumulating in the skin. Can range from mild to severely disabling and is treated with a stepwise medication ladder.

• Rifampicin (rifampin) — an antibiotic with potent anti-itch properties used second-line for PBC-related pruritus. Starts at 150 mg/day; requires liver-test monitoring due to rare drug-induced liver injury. Turns body fluids orange.
• UK-PBC score — a validated risk calculator developed from the UK national PBC registry of over 8,000 patients; estimates the risk of liver transplant or death at 5, 10, and 15 years after starting UDCA.
• Ursodiol / UDCA (ursodeoxycholic acid) — the cornerstone first-line treatment for PBC since the 1990s. A naturally occurring bile acid taken by mouth (13–15 mg/kg/day) that replaces toxic bile acids, reduces inflammation, and slows disease progression. Lifelong therapy.
• Variceal bleeding — bleeding from enlarged veins (varices) in the esophagus or stomach, caused by portal hypertension from cirrhosis. A medical emergency requiring immediate treatment. Patients with cirrhosis are screened for varices by endoscopy.