Six key characteristics to consider when treating PBC
See how age, sex, race, symptoms, PBC history, and comorbidities could impact PBC treatment decisions
AGE
Younger patients are less likely to respond to UDCA and may have more aggressive and harder-to-treat PBC2,a,b
Patients with PBC
<40 years of age
<40years of age
were symptomatic, with more severe pruritus and fatigue2,a
aPatients (N=2353) from a UK-PBC patient research cohort were analyzed in a cross-sectional study to obtain a better understanding of PBC phenotypes and differences including response to UDCA and impact of symptoms of disease based on age and sex.2
bAASLD (2018) and EASL (2017) PBC treatment guidelines recommend UDCA as first-line treatment for patients with PBC.3,4
SEX
Men with PBC are significantly less likely to respond to UDCA1,2,c
The odds of PBC occurring in men were up to
2.5 x greater
than have been previously estimated1
Men often presented with more advanced PBC, putting them at risk of end-stage liver disease1
cPatients (N=2353) from a UK-PBC patient research cohort were analyzed in a cross-sectional study to obtain a better understanding of PBC phenotypes and differences including response to UDCA and impact of symptoms of disease based on age and sex.2
RACE & ETHNICITY
Black, Hispanic, and Indigenous patients with PBC may be more likely to have an inadequate response to UDCA1,6,d-g
Black and Hispanic patients presented with PBC at younger ages and had more aggressive disease progression1,2,5,d,f
dPatients (N=2353) from a UK-PBC patient research cohort were analyzed in a cross-sectional study to obtain a better understanding of PBC phenotypes and differences including response to UDCA and impact of symptoms of disease based on age and sex.2
eThe prevalence, characteristics, predictors, outcomes, and trends (among gender and racial categories) of hospitalizations for PBC were explored in a retrospective descriptive epidemiological study using the National Inpatient Sample database from 2007-2014. ICD-9-CM codes were used to identify primary PBC hospitalizations (N=8460).5
fWhile Hispanic patients were shown to have poorer responses to UDCA compared with White patients, these results did not translate to poorer outcomes after multivariate adjustment.5
gTo investigate PBC epidemiology and treatment within geographically and racially diverse populations of patients, patient cases (N=4241) from the Fibrotic Liver Disease Consortium during the years 2003-2014 were analyzed to determine the effects of factors associated with PBC prevalence and treatment with UDCA.6
SYMPTOMS
Symptoms of PBC, including pruritus, are not typically relieved with UDCA3
In a cross-sectional study of patients with PBC (N=225)7,h:
89%
self-reported pruritus (n=200/225)7
but only
39%
had pruritus recently documented in their medical records (n=88/225)7
In a retrospective, cross-sectional study of patients with PBC8,i:
34%
more patients with PBC-related pruritus reported fatigue vs those who did not have pruritus (26.6% vs 19.9%)
hA cross-sectional, noninterventional study (N=225) evaluated the prevalence of patient-reported pruritus vs pruritus documented in medical records. The overlap between individuals with patient-reported and medical record–documented pruritus in relation to pruritus severity was also evaluated.7
iThe prevalence of prespecified comorbidities and medications in a PBC population (n=1963), a PBC-pruritus subpopulation (n=139), and a noncase population (n=10,245,592) was assessed over a 12-month period in a retrospective, cross-sectional study using data from the IBM MarketScan Commercial Claims and Medicare Supplemental Database.8
PBC HISTORY
1L treatment with UDCA may not achieve biochemical response3,4
For patients with PBC taking UDCA:
upto
50% experienced inadequate biochemical response4,j
upto
50%
experienced inadequate biochemical response4,j
In a multicenter meta-analysis by the GLOBAL PBC Study Group of patients with PBC taking UDCA (N=4119)10,k:
~32%
had stage III or IV fibrosis
jBiochemical response is a prognostic tool for PBC that can be defined by several published criteria. One criterion that has been used in clinical trials defines response to treatment at 12 months as ALP <1.67 x ULN, ≥15% decrease in ALP from baseline, and TB ≤1 x ULN. Conversely, patients who do not meet the criteria thresholds are considered to have an inadequate biochemical response and may remain at risk for disease progression.3,11
kIn an international, multicenter meta-analysis of patients with PBC who were treated with UDCA at liver centers in 8 European and North American countries, histological disease stage was available for 1642 patients using baseline biopsies obtained within 1 year of starting UDCA. Of those patients, 541 (32%) had stage III or IV fibrosis.10
COMORBIDITIES & CONCOMITANT MEDICATIONS
Consider drug-to-drug interactions when choosing a second-line treatment3,4
Patients with PBC may be managing a number of comorbid conditions including, but not limited to3,12:
Hyperlipidemia
up to
95%
Portal hypertension
~33%
in patients with stage III or IV fibrosis
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1L=first line; AASLD=American Association for the Study of Liver Diseases; ALP=alkaline phosphatase; EASL=European Association for the Study of the Liver; PBC=primary biliary cholangitis; TB=total bilirubin; UDCA=ursodeoxycholic acid; ULN=upper limit of normal.
Tap for Important Safety Information, including warnings for fractures, liver test abnormalities, and biliary obstruction
LIVDELZI is indicated for the treatment of primary biliary cholangitis (PBC), in combination with ursodeoxycholic acid (UDCA) in adults who have had an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA.
This indication is approved under accelerated approval based on a reduction of alkaline phosphatase (ALP). Improvement in survival or prevention of liver decompensation events have not been demonstrated. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
Limitation of Use: Use of LIVDELZI is not recommended in patients who have or develop decompensated cirrhosis (eg, ascites, variceal bleeding, hepatic encephalopathy).
IMPORTANT SAFETY INFORMATION
Warnings and Precautions
- Fractures: Fractures occurred in 4% of LIVDELZI-treated patients compared to no placebo-treated patients. Consider the risk of fracture in the care of patients treated with LIVDELZI and monitor bone health according to current standards of care.
- Liver Test Abnormalities: LIVDELZI has been associated with dose-related increases in serum transaminase (AST and ALT) levels >3x ULN in patients receiving 50 mg and 200 mg once daily (5x and 20x higher than the recommended dosage of 10 mg once daily). Perform baseline clinical and laboratory testing when starting LIVDELZI and monitor thereafter according to routine patient management. Interrupt treatment if the liver tests (ALT, AST, total bilirubin, and/or ALP) worsen, or if the patient develops signs and symptoms of clinical hepatitis (eg, jaundice, right upper quadrant pain, eosinophilia). Consider permanent discontinuation if liver tests worsen after restarting LIVDELZI.
- Biliary Obstruction: Avoid use of LIVDELZI in patients with complete biliary obstruction. If biliary obstruction is suspected, interrupt LIVDELZI and treat as clinically indicated.
Adverse Reactions
- The most common adverse reactions (≥5%) with LIVDELZI were headache (8%), abdominal pain (7%), nausea (6%), abdominal distension (6%), and dizziness (5%).
Drug Interactions
Potential Increased Exposure of LIVDELZI with:
- Probenecid: Avoid coadministration with LIVDELZI.
- Strong CYP2C9 Inhibitors: Monitor for adverse effects during concomitant use.
- Dual Moderate CYP2C9 and Moderate or Strong CYP3A4 Inhibitors (eg, fluconazole): Monitor for adverse effects during concomitant use.
- CYP2C9 Poor Metabolizers Using Moderate or Strong CYP3A4 Inhibitors: Monitor for adverse effects during concomitant use of a moderate or strong CYP3A4 inhibitor in patients who are CYP2C9 poor metabolizers.
- Dual or Multiple Clinical Inhibitors of Drug Transporters OATP1B1, OATP1B3, and BCRP (eg, cyclosporine): Monitor for adverse effects during concomitant use.
Potential Reduction in LIVDELZI Exposure with:
- Rifampin: Concomitant use of LIVDELZI with rifampin, an inducer of metabolizing enzymes, may result in delayed or suboptimal LIVDELZI biochemical response. Monitor biochemical response (eg, ALP and bilirubin) when patients initiate rifampin during LIVDELZI treatment.
- Bile Acid Sequestrants: Administer LIVDELZI at least 4 hours before or 4 hours after taking a bile acid sequestrant, or at as great an interval as possible.
Pregnancy and Lactation
- Pregnancy: There are insufficient data from human pregnancies exposed to LIVDELZI to allow an assessment of a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Report pregnancies to Gilead Sciences, Inc., at 1-800-445-3235.
- Lactation: There are no data on the presence of LIVDELZI in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for LIVDELZI and any potential adverse effects on the breastfed infant from LIVDELZI.
Please see full Prescribing Information for LIVDELZI.
References
- Trivella J, John BV, Levy C. Primary biliary cholangitis: epidemiology, prognosis, and treatment. Hepatol Commun. 2023;7(6):e0179. doi:10.1097/HC9.0000000000000179
- Carbone M, Mells GF, Pells G, et al. Sex and age are determinants of the clinical phenotype of primary biliary cirrhosis and response to ursodeoxycholic acid. Gastroenterology. 2013;144(3):560-569.e7. doi:10.1053/j.gastro.2012.12.005
- Lindor KD, Bowlus CL, Boyer J, Levy C, Mayo M. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419. doi:10.1002/hep.30145
- European Association for the Study of the Liver. EASL Clinical Practice Guidelines: the diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017;67(1):145-172. doi:10.1016/j.jhep.2017.03.022
- Adejumo AC, Akhtar DH, Dennis BB, et al. Gender and racial differences in hospitalizations for primary biliary cholangitis in the USA. Dig Dis Sci. 2021;66(5):1461-1476. doi:10.1007/s10620-020-06402-3
- Lu M, Li J, Haller IV, et al; FOLD Investigators. Factors associated with prevalence and treatment of primary biliary cholangitis in United States health systems. Clin Gastroenterol Hepatol. 2018;16(8):1338-1341.e6. doi:10.1016/j.cgh.2017.10.018
- Gungabissoon U, Smith HT, von Maltzahn R, et al. Pruritus in primary biliary cholangitis is under-recorded in patient medical records. BMJ Open Gastroenterol. 2024;11(1):e001287. doi:10.1136/bmjgast-2023-001287
- Gungabissoon U, Gibbons DC, Requena G, Ribeiro de Souza A, Smith H. Disease burden of primary biliary cholangitis and associated pruritus based on a cross-sectional US claims analysis. BMJ Open Gastroenterol. 2022;9(1):e000857. doi:10.1136/bmjgast-2021-000857
- Koc OM, Toussaint AK, Untas A, et al. Fatigue in people with primary biliary cholangitis: a position paper from the European Reference Network for Rare Liver Diseases. Lancet Gastroenterol Hepatol. 2026;11(1):71-86. doi:10.1016/S2468-1253(25)00257-2
- Lammers WJ, Hirschfield GM, Corpechot C, et al; Global PBC Study Group. Development and validation of a scoring system to predict outcomes of patients with primary biliary cirrhosis receiving ursodeoxycholic acid therapy. Gastroenterology. 2015;149(7):1804-1812.e4 doi:10.1053/j.gastro.2015.07.061
- Hirschfield GM, Bowlus CL, Mayo MJ, et al; RESPONSE Study Group. A phase 3 trial of seladelpar in primary biliary cholangitis. N Engl J Med. 2024;390(9):783-794. doi:10.1056/NEJMoa2312100
- Carey EJ, Ali AH, Lindor KD. Primary biliary cirrhosis. Lancet. 2015;386(10003):1565-1575. doi:10.1016/s0140-6736(15)00154-3