Gastroenterology
Scratching at the Surface or Soothing the Itch: Understanding the Challenges of Primary Biliary Cholangitis: A Case Study Approach
This interactive case study was organised and funded by GSK.
START
NX-GBL-HP-WCNT-240004 | June 2025
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Within this interactive case study, the case of a 45-year-old patient who has been diagnosed with primary biliary cholangitis (PBC) will be explored. The case study shares details of the patient’s medical history, treatment, and symptom management. Through interactive questions, you’ll have a chance to test your knowledge before learning about the patient’s next steps and outcomes.
Understanding the Challenges of Primary Biliary Cholangitis: A Case Study Approach
Disclosure
Disclaimer
This interactive case study was developed with support from David Jones, Professor of Liver Immunology, Newcastle University; Honorary Consultant Hepatologist, Newcastle Hospitals NHS Foundation Trust, UK.
This is a hypothetical patient case and outcomes may not be reflective of clinical studies or real-life circumstances. This includes reference to agents that may be used off-label or for unlicensed indications. The mention of these agents and their uses is intended solely for educational purposes and should not be considered an endorsement or recommendation for their use outside approved indications. Please always consult guidelines and local prescribing information in your country of practice, as information may vary.
3/19
PBC Question 1: Which of these statements about PBC is most accurate?
It affects around 10,000 patients in the UK
It can progress to cirrhosis but rarely causes symptoms
It is more aggressive in younger patients but rarely affects children
There is no licensed 1st line therapy
A
B
C
D
Burke L et al. Frontline Gastroenterol. 2022;14(2):175. Hirschfield GM. Best Pract Res Clin Gastroenterol. 2011;25(6):701-12. Liberal R et al. Dig Liver Dis. 2019;52(7):1064-65.
4/19
PBC Question 2: Which of these statements about PBC is most accurate?
The characteristic liver biopsy finding is granulomatous cholangitis
The majority of patients with PBC will eventually die of the condition
PBC spontaneously resolves in about 20% of patients
It can be a challenge to make the diagnosis of PBC
European Association for the Study of the Liver (EASL). J Hepatol. 2017;67(1):145-72.
Background (PBC)
Hirschfield GM et al. Gut. 2018;67:1568-94.
Disease: Chronic cholestatic liver disease with intrahepatic bile duct injury and eventual loss. Autoimmunity and anti-mitochondrial antibodies are almost universal. Anti-nuclear antibodies can also be seen but have distinct patterns. Has both genetic and environmental risk factors. Prevalence is 40/100,000 in the UK.
Patient Impact: Slowly progresses to biliary cirrhosis. Symptoms can be present throughout the disease course (fatigue and itch). These do NOT correlate with disease severity and are the major issue for many patients. Stratified, step-wise approach to therapy starting with ursodeoxycholic acid (UDCA).
Histopathological features of PBC
5/19
Patient Background
Disease: 45 years old; female; body weight of 61 Kg Mother of two teenage children Two elderly and quite dependent parents Works as a teacher of 8–9 year-olds who can be “really hard work” Had cholestasis of pregnancy in her first pregnancy Non-drinker Non-smoker (gave up 2 years ago)
Family History
6/19
Mother has thyroid disease (underactive)
Great-grandmother probably died of liver disease (jaundice and prominent itching)
Patient Presentation
Went to the general practitioner (GP) with itching on her scalp, hands, and feet. Felt like “creepy crawlies under the skin.” Puzzled because she hasn’t got a rash, other than where she has damaged the skin by scratching. Itch was now beginning to interfere with her sleep. Getting progressively more exhausted but thought it was a result of not sleeping. Work was a struggle even with a fixed timetable. Does not have the energy to go out anymore and was worried that her relationship with her husband was suffering as a result. Beginning to get worried that there was “something badly wrong.” GP was not confident about the diagnosis, so ordered a series of blood tests.
7/19
8/19
Itch question: Which of the following can cause itch? Tick all that can apply.
Systemic sclerosis
Cholestatic liver disease
Chronic renal failure
Lymphoma
Cheng AY, Wong LS. Diagnostics (Basel). 2022;12(5):1108. Kim JC et al. Int J Mol Sci. 2023;24(2):1559. Hegade VS et al. Clin Gastroenterol Hepatol. 2019;17:1379-87. Rowe B, Yosipovitch G. Eur J Pain. 2016;20:19-23.
SUBMIT
9/19
PBC Diagnosis Question The characteristic diagnostic test in PBC is:
The anti-nuclear antibody.
Alanine transaminase (ALT) is more elevated than alkaline phosphatase (ALP).
IgM is more likely to be elevated than IgG.
Biopsy is necessary to diagnose PBC.
Hirschfield GM et al. Gut. 2018;67(9):1568-94. Hirschfield GM. Best Pract Res Clin Gastroenterol. 2011;25(6):701-12.
Diagnosis
LFT
10/19
Immunology
Ultrasound
Fibroscan
Jones DEJ. J Clin Path. 2000;53:1-8.
Multiple nuclear dot pattern by indirect immunofluorescence
Alkaline phosphatase 483 IU/L Bilirubin 15 mg/dL Alanine transaminase 45 IU/L Albumin 40 g/L
Anti-smooth muscle antibody (AMA) 1:640 Anti-nuclear antibody (ANA) 1:80 (multiple nuclear dot pattern) IgG 17.0 g/L IgM 4.5 g/L
Slightly enlarged liver No spleen enlargement
11 Kpa
11/19
Treatment Question 1: How would you approach treatment?
*Consult product SmPC before initiating. Hirschfield GM et al. Gut. 2018;67(9):1568-94. Rudic JS et al. Cochrane Database Syst Rev. 2012;12(12):CD000551.
Recheck liver function tests in 6 months to ensure diagnosis before deciding
Don’t treat until evidence of progressive fibrosis is seen
Begin ursodeoxycholic acid (UDCA) at 13–15 mg/Kg*
Begin UDCA at 8–12 mg/Kg
12/19
Treatment Question 2: Which of the following is a suitable treatment option for itch?
First-line treatment is with cholestyramine 4 g x three times a day*
There is no need to treat the itch specifically, as it will improve with UDCA
Try antihistamines if cholestyramine is not effective
Rifampicin 150 mg/day is an alternative first-line therapy
*Consult product SmPC before initiating. Hirschfield GM et al. Gut. 2018;67(9):1568-94. Levy C et al. Gastroenterol Hepatol. 2023;21(8):2076-87.
13/19
Treatment Question 3: Which of the following is true?
UDCA is effective in 60% of patients
An alkaline phosphatase of 165 IU/L after 1 year of UDCA is an indication for second-line therapy
Obeticholic acid used as a second-line therapy will improve itch
Obeticholic acid has been shown in trials to improve survival
Hirschfield GM et al. Gut. 2018;67(9):1568-94. Kowdley K et al. Am J Gastroenterol. 2024;DOI:10.14309/ajg.0000000000003029. Pate J et al. BMJ Open Gastroenterol. 2019;6(1):e000256. Murillo Perez CF et al. Gastroenterology. 2022;163(6):1630-42.e3.
14/19
Treatment
Beza: bezafibrate; OCA: obeticholic acid.
Disease control: UDCA started at 1,000 mg/day (14 mg/Kg). Alkaline phosphatase down to 350 IU/L after 1 year. Bezafibrate started (400 mg sustained-release tablet daily). Alkaline phosphatase improved to 280 IU/L. Obeticholic acid started at 5 mg/day.
Itch control: UDCA led to no change in itch. Obeticholic acid was not used as initial second-line therapy because of itch severity. Bezafibrate controlled itch but did not give a full response Obeticholic acid was tolerated with bezafibrate.
Nevens F et al. NEJM. 2016;375:631-43. Corpechot C et al. NEJM. 2018;378:2171-81.
15/19
Patient Outcome
Disease control: Alkaline phosphatase reduced to 175 IU/L with obeticholic acid/bezafibrate/UDCA. Has remained stable for 2 years now. Fibroscan has progressively improved (now 8.7). No issues with tolerating the drugs.
Quality of life: Itch was controlled with Bezafibrate, UDCA, and obeticholic acid. Was then tolerated fine with no itch (it’s recognised side effect). Itch now is rated 2/10 by the patient who is sleeping better. Fatigue is still a problem. Still struggling at work and at home. Interested in trials/research aimed at addressing fatigue.
16/19
Questions to Ask Yourself (and the Patient)
Is it a PBC itch?
Hegade VS et al. Clin Med. 2015;15:351-7.
Character (creepy crawlies under the skin) Distribution (palms of the hand, soles of the feet, scalp)
How bad is it?
Simple numerical rating scale (0–10) Severity assessment tools (research)
Are there knock-ons?
Sleep disturbance Depression Social isolation
Does it need treatment?
Largely a patient decision
What agent?
Cholestyramine Rifampicin Bezafibrate Others
17/19
Key Takeaway
PBC is an important cause of chronic liver disease in women and should be suspected whenever ALP is elevated in this group. Diagnosis is usually simple and is based on 2 out of 3, elevated ALP, AMA, and compatible liver biopsy. In most patients, diagnosis is on the first work-up, and a biopsy isn’t needed. UDCA therapy is the first line with a step up to obeticholic acid or bezafibrate if the response is inadequate. Itch and/or fatigue are common and are a major issue for patients. They typically do not improve with PBC disease-modifying therapy. There are specific therapies for itch. There are no drug treatments for fatigue. Progression to end-stage liver disease is now very rare other than in later-presenting patients. Be aware of all patients with elevated bilirubin. If in doubt, discuss with a transplant unit.
18/19
Most Frequent Symptoms of PBC - Practical Management Tips -
*Unlicensed/ Off-label use of medicine are not officially approved for treatment. Please check your local guidelines before prescribing. PPAR: peroxisome proliferator-activated receptors.
Fatigue
Pruritus
Sicca complex
Bone or joint aches
Abdominal pain, right upper quadrant
Anxiety and depression
Social isolation
Focus on coping Exercise, pacing your day
Avoid hot showers, sharp nails, and dry skin No antihistamines Medical treatment option: PPAR agonists (fenofibrate/bezafibrate)* Bile acid sequestrants/rifampicin Naltrexone/sertraline Consider trials
Artificial tears
Acetaminophen* can be used Explain varying course over time
Reassurance with respect to impact on natural history
Explain the course of PBC for the individual patient Reassure if possible, be fair if needed Psychological support
Proactively mention this possibility Communicate about your disease/join patient association
19/19
THANK YOU
