In adult patients with cholestasis and no likelihood of systemic disease, a diagnosis of PBC can be made based on elevated ALP and the presence of AMA.^1–5 High IgM concentrations do not form part of standard diagnostic paradigms but can be useful in making a clinical diagnosis in patients with other atypical features.² Elevation of serum IgG can be a feature of the presence of additional autoimmune hepatitis-like features in PBC; it is also more commonly reported in AMA-negative series. Elevated IgG can also be a reflection of advanced fibrosis/cirrhosis generally.²  gGT determination is not used to reach a diagnosis or guide therapy, although there is a strong correlation between gGT and ALP.² Elevation in bilirubin is characteristic of advanced disease; it is also an important prognostic marker.²

Abbreviations

ALP, alkaline phosphatase; AMA, anti-mitochondrial antibody; gGT, gamma-glutamyl transferase; Ig, immunoglobulin; PBC, primary biliary cholangitis.

References

1. Hirschfield GM, et al. Expert Rev Gastroenterol Hepatol. 2021;15:929–39.
2. Hirschfield GM, et al. Gut. 2018;67:1568–94.
3. European Association for the Study of the Liver. J Heptatol. 2017;67:145–72.
4. You H, et al. Hepatol Int. 2022;16:1–23.
5. Lindor KD, et al. Hepatology. 2019;69:394–419.

Fibrates are currently used off-label for treating PBC.¹ They can be used in combination with either UCDA or OCA, or with both as a triplet therapy (UDCA+OCA+fibrate).² Available data for triplet therapy demonstrate how it may normalize biochemical liver tests and improve pruritus in patients with difficult-to-treat PBC.³ Data suggest the optimal dose for UDCA is 13–15 mg/kg/day with no benefit observed from increasing the dose to 23–25 mg/kg/day.⁴ The maximum recommended dose for OCA is 10 mg/day.^5,6

Abbreviations

OCA, obeticholic acid; PBC, primary biliary cholangitis; UDCA, ursodeoxycholic acid.

References

1. Alvaro D, et al. Liver Int. 2020;40:2590–601.
2. Floreani A, et al. Biomedicines. 2022;10:2033.
3. Soret P-A, et al. Aliment Pharmacol Ther. 2021;53:1138–46.
4. Hirschfield GM, et al. Gut. 2018;67:1568–94.
5. FDA. Obeticholic acid PI. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2022/207999s008lbl.pdf (accessed 24 November 2022).
6. EMA. Obeticholic acid SmPC. Available at: www.ema.europa.eu/en/documents/product-information/ocaliva-epar-product-information_en.pdf (accessed 24 November 2022).

Based on a patient cohort from the GLOBAL PBC Study Group (time zero, n=2,281; time 1 year, n=2,555), who were UDCA-treated and untreated, the 10-year survival in patients with ALP ≤1 × ULN or ALP 1.0–1.67 × ULN was 93.2% and 86.1%, respectively. The 10-year survival rates of patients with bilirubin ≤0.6 × ULN and >0.6 × ULN were 91.3% and 79.2%, respectively. Targeting normal ALP or bilirubin levels ≤0.6 × ULN is thus likely to optimize outcomes in patients with PBC.

Abbreviations

ALP, alkaline phosphatase; PBC, primary biliary cholangitis; UDCA, ursodeoxycholic acid; ULN, upper limit of normal.

Reference

Murillo Perez CF, et al. Am J Gastroenterol. 2020;115:1066–74.

Although clinical management is important for the disease course and physical symptoms, research suggests individualized support, driven by a formal assessment of patients’ needs rather than by assumptions regarding prognosis should be offered.¹ Health literacy and resultant patient empowerment is particularly important in PBC where clinicians may be less familiar treating it.² Healthcare professionals should encourage patients to seek support in different patient associations or organisations for access to additional support outside the healthcare setting.¹ Patients should be offered the opportunity to participate in clinical trials if they fall into targeted groups.³

Abbreviation

PBC, primary biliary cholangitis.

References

1. Grønkjær LL, Lauridsen MM. JHEP Reports. 2021;3:100370.
2. Leighton J, et al. Frontline Gastroenterol. 2021;12:370–3.

Patients with PBC tend to lead sedentary lives due to fear of exacerbating their fatigue, but muscle fatigability is increased when physical activity is reduced.¹ There is no evidence to suggest that exercise is harmful in PBC-related fatigue, and there are pilot data to suggest that structured exercise initiated at tolerable levels may be beneficial;² markers of muscle fatigue were improved with repeated single exercise episodes.^1,3 Trials with modafinil in PBC suggest it has no impact on fatigue versus placebo.⁴

Abbreviation

PBC, primary biliary cholangitis.

References

1. Lynch EN, et al. World J Hepatol. 2022;14:1111–19.
2. Hirschfield GM, et al. Gut. 2018;67:1568–94.
3. Hollingsworth KE, et al. J Hepatol. 2010;53:155–61.
4. Silveira MG,et al. Am J Ther. 2017; 24:e167–76.