Primary biliary cholangitis is an autoimmune cholestatic liver disease characterized by progressive destruction of bile ducts, which can ultimately progress to chronic liver disease and cirrhosis. Ursodeoxycholic acid and obeticholic acid are the only 2 Food and Drug Administration (FDA)-approved medications for primary biliary cholangitis. Unfortunately, up to 40% of patients with primary biliary cholangitis have an incomplete response to ursodeoxycholic acid, warranting an essential need for additional therapeutics. Peroxisome proliferator-activated receptor agonists have shown promising data supporting their use as disease-modifying therapies. Fibroblast growth factor-19 agonists, farnesoid X receptor agonists, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 3 inhibitors are additional agents under investigation as potential disease-modifying therapy. However, evidence supporting the use of certain novel therapies over others is sparse. There is a need for additional clinical trials as well as research aimed at the underlying pathophysiology of primary biliary cholangitis to discover additional therapeutic targets. Cite this article as: Barba Bernal R, Ferrigno B, Medina Morales E, et al. Management of primary biliary cholangitis: Current treatment and future perspectives. Turk J Gastroenterol. 2023;34(2):89-100.

Goals: We aim to summarize the current management of pruritus in primary biliary cholangitis (PBC) by evaluating the efficacy and safety of pharmacological therapies. Background: Pruritus is a common symptom of PBC, and evidence regarding the most effective antipruritic agents available is lacking. New pharmacotherapy for PBC has shown promising antipruritic effects. Study: We performed a systematic literature review and meta-analysis including all available double-blind, randomized, placebo-controlled clinical trials that evaluated the efficacy of pharmacotherapy for the symptomatic management of pruritus in PBC. Pruritus was assessed as either a change from baseline or a postintervention score. Results: We included 33 studies and 20 medications. Using the visual analog scale, cholestyramine did not significantly improve pruritus compared with placebo [standardized mean differences (SMD): −0.94, 95% CI: −2.05 to 0.17], whereas rifampin and nalfurafine hydrochloride both significantly improved pruritus (SMD: −3.29, 95% CI: −5.78 to −0.80; n=23 and SMD: −0.58, 95% CI: −1.04 to −0.12). In addition, Bezafibrate and linerixibat significantly improved pruritus (SMD: −1.05, 95% CI: −1.41 to −0.68; n=110 and SMD: −0.31, 95% CI: −0.62 to −0.04, respectively). This effect was also present within the subgroup analysis by pruritus scale, where both bezafibrate and linerixibat significantly improved pruritus compared with placebo (SMD: −1.09, 95% CI: −1.54 to −0.65; P<0.001; visual analog scale; as postintervention score and SMD: −0.31, 95% CI: −0.62 to −0.01; P=0.04; numeric rating scale; as a change from baseline score, respectively). Conclusions: Bezafibrate and Linerixibat are potential second-line antipruritic medications for PBC, particularly those with moderate to severe pruritus.

Primary sclerosing cholangitis (PSC) is the leading indication of liver transplantation (LT) among autoimmune liver disease patients. There is a scarcity of studies comparing survival outcomes between living-donor liver transplants (LDLT)s and deceased-donor liver transplants (DDLTs) in this population. Using the United Network for Organ Sharing database, we compared 4679 DDLTs and 805 LDLTs. Our outcome of interest was post-LT patient survival and post-LT graft survival. A stepwise multivariate analysis was performed, adjusting for recipient age, gender, diabetes mellitus, ascites, hepatic encephalopathy, cholangiocarcinoma, hepatocellular carcinoma, race, and the model for end-stage liver disease (MELD) score; donor’ age and sex were also included to the analysis. According to univariate and multivariate analysis, LDLT had a patient and graft survival benefit compared to DDLT (HR, 0.77, 95% CI 0.65–0.92; p < 0.002). LDLT patient survival (95.2%, 92.6%, 90.1%, and 81.9%) and graft survival (94.1%, 91.1%, 88.5%, and 80.5%) at 1, 3, 5, and 10 years were significantly better than DDLT patient survival (93.2%, 87.6%, 83.3%, and 72.7%) and graft survival (92.1%, 86.5%, 82.1%, and 70.9%) (p < 0.001) in the same interval. Variables including donor and recipient age, male recipient gender, MELD score, diabetes mellitus, hepatocellular carcinoma, and cholangiocarcinoma were associated with mortality and graft failure in PSC patients. Interestingly, Asians were more protected than Whites (HR, 0.61; 95% CI, 0.35–0.99; p < 0.047), and cholangiocarcinoma was associated with the highest hazard of mortality (HR, 2.07; 95% CI, 1.71–2.50; p < 0.001) in multivariate analysis. LDLT in PSC patients were associated with greater post-transplant patient and graft survival compared to DDLT patients.

Autoimmune liver diseases such as autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis are the primary indication for ∼24% of total liver transplants. The liver transplant allocation system is currently based upon the Model for End-Stage Liver Disease and it often underestimates the severity of autoimmune liver diseases. We aim to compare the rate of adverse waitlist removal among patients with all autoimmune liver diseases and other indications for liver transplant in the Model for End-Stage Liver -Na era. Using the United Network for Organ Sharing database, we identified all patients listed for liver transplant from 2016 to 2019. The outcome of interest was waitlist survival defined as the composite outcome of death or removal for clinical deterioration. Competing risk analysis was used to evaluate the waitlist survival. Patients with autoimmune hepatitis had a higher risk of being removed from the waitlist for death or clinical deterioration (SHR 1.37, 95% CI 1.08-1.72; P<0.007), followed by primary biliary cholangitis (SHR 1.34, 95% CI 1.07-1.68; P<0.011). High waitlist death or removal for clinical deterioration was observed in patients with PBC and AIH when compared to other etiologies. It may be useful to reassess the process of awarding MELD exception points to mitigate such disparity.

Autoimmune liver diseases (AILDs) affect health-related quality of life (HRQOL). This seven-year, prospective study analyzes the impact of AILDs on HRQOL. We collected the Chronic Liver Disease Questionnaire (CLDQ) and the EuroQol-5 Dimension (EQ-5D), totaling 1,214 responses from 466 AILD patients (2017-2024). CLDQ was compared via Kruskal-Wallis. Chi-square and ANOVA were used for EQ-5D frequencies and means. Multivariate (MVA) regressions identified CLDQ symptom predictors. Tobit regression analyzed EQ-5D UI. Pearson's correlation assessed CLDQ-EQ-5D association. We included 230 AIH, 118 PSC, and 118 PBC patients. Total CLDQ was lower in PBC compared to AIH and PSC (5.25, 5.54, 5.59; P<0.001), as was EQ-5D UI (0.85, 0.88, 0.88; P<0.001). In CLDQ, PBC domains were significantly worse except Worry. Fatigue scored lowest in PBC, with tiredness, decreased energy, and daytime sleepiness as the most debilitating symptoms (3.91, 4.20, 4.27; P<0.001). In EQ-5D, every item was worse in PBC except anxiety/depression, with pain being worst (P<0.001). CLDQ MVA identified female (β: -0.26), Hispanic race (β: -0.31), and MASLD/MASH (β: -0.32) as predictors of symptom worsening (P<0.05). Tobit regression for EQ-5D revealed female (β: -0.03), MASLD/MASH (β: -0.07), and cirrhosis (β: -0.06) as symptom severity predictors (P<0.05). Pearson's correlation showed that CLDQ and EQ-5D in AILD were strongly correlated (r = 0.63; P<0.001). Among AILDs, PBC most severely impacts HRQOL, especially in tiredness, sleepiness, concentration, and pain. Female, Hispanic, and MASLD overlap patients are disproportionately affected. Both CLDQ and EQ-5D predict symptom severity, but CLDQ identifies more predictors and stronger associations.

Background: The cornerstone treatment for primary biliary cholangitis (PBC) is ursodeoxycholic acid (UDCA), but many patients exhibit an incomplete response, leading to disease progression. Risk prediction models like the GLOBE and UK-PBC scores hold promise for patient stratification and management. We aimed to independently assess the predictive accuracy of these risk scores for UDCA response in a prospective U.S. cohort. Methods: We conducted a prospective cohort study at a U.S. liver center, monitoring UDCA-treated PBC patients over a one-year follow-up. We evaluated the predictive efficacy of the GLOBE and UK-PBC scores for UDCA treatment response, comparing them to the Paris II criteria. Efficacy was assessed using univariate and multivariate analyses, followed by prognostic performance evaluation via receiver operating characteristic (ROC) curve analysis. Results: We evaluated 136 PBC patients undergoing UDCA therapy. Based on the Paris II criteria, patients were categorized into UDCA full-response and non-response groups. The GLOBE score identified a non-responder rate of 18% (p = 0.205), compared to 20% (p = 0.014) with the Paris II criteria. Multivariate analysis, adjusted for age and biochemical markers, showed that both the GLOBE and UK-PBC scores were strongly associated with treatment response (p < 0.001). The area under the ROC curve was 0.87 (95% CI 0.83−0.95) for the GLOBE score and 0.94 (95% CI 0.86−0.99) for the UK-PBC risk score. Conclusions: Our study demonstrates that GLOBE and UK-PBC scores effectively predict UDCA treatment response in PBC patients. The early identification of patients at risk of an incomplete response could improve treatment strategies and identify patients who may need second-line therapies.