Ocaliva (obeticholic acid) / Sumitomo Pharma, Intercept - LARVOL DELTA

Efficacy, symptoms, and safety of second-line PBC therapies: a network meta-analysis. (PubMed, Front Pharmacol) - "The therapeutic landscape for primary biliary cholangitis (PBC) with an inadequate response to ursodeoxycholic acid (UDCA) is rapidly evolving...We included randomized controlled trials (RCTs) with durations of 12-52 weeks evaluating PPAR agonists (bezafibrate, seladelpar, elafibranor, saroglitazar), farnesoid X receptor (FXR) agonists (obeticholic acid [OCA]), and IBAT inhibitors (linerixibat) against placebo/UDCA...While bezafibrate offers unparalleled potency for POISE criteria, seladelpar 10 mg provides the most advantageous clinical balance, achieving deep biochemical remission (ALP normalization) alongside profound pruritus relief and a favorable safety profile. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=261351, identifier 420261351426."

Journal • Retrospective data • Review • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

Obeticholic Acid and Edaravone Protect Against Cisplatin-Induced Hepatotoxicity Through Modulation of Keap1/Nrf2/ARE, TNF-α/NF-κB, and AKT/GSK-3β Pathways. (PubMed, J Biochem Mol Toxicol) - "The study highlights the role of key molecular pathways, including Keap1/Nrf2/HO-1,HO-1, TNF-α/NF-κB, and AKT/GSK-3β, in the hepatoprotective mechanisms of OCA. Collectively, these findings suggest that OCA and EDA, particularly in combination, attenuate CP-induced hepatotoxicity and are associated with coordinated modulation of oxidative stress, inflammatory signaling, and AKT/GSK-3β-associated pro-survival/pro-death pathways."

Journal • Hepatology • Inflammation • KEAP1 • TNFA

FXR agonist in post-liver transplantation patients: a randomized open-labeled study. [Protocol]. (PubMed, F1000Res) - "Current medical therapies for post-LT cholestasis are limited, with ursodeoxycholic acid (UDCA) frequently used, despite questionable efficacy. Obeticholic acid (OCA), a potent Farnesoid X Receptor (FXR) agonist approved by the FDA for treating primary biliary cholangitis (PBC), has shown potential benefits in reducing elevated cholestatic liver enzymes...Secondary outcomes include molecular markers, biliary complications, graft rejection, quality of life, and cost-effectiveness. Results are anticipated to demonstrate that OCA could ameliorate cholestasis, improve graft survival, reduce post-transplant complications, and enhance quality of life, potentially setting a new standard in post-LT care if found beneficial."

Journal • Cardiovascular • Cholestasis • Fibrosis • Hepatology • Immunology • Infectious Disease • Liver Cancer • Oncology • Primary Biliary Cholangitis • Reperfusion Injury • Solid Tumor • Transplant Rejection • Transplantation

Mechanism of FXR signaling: from liver inflammation to hepatocellular carcinoma. (PubMed, Biochem Biophys Rep) - "Agonists like INT-767 block progression from chronic hepatitis to fibrosis/cirrhosis (2) In HCC, FXR dysfunction (e.g., HBx C40-mediated)...Quercetin and obeticholic acid suppress tumor growth via FXR signaling...FXR-targeting agonists, natural compounds, and combination immunotherapy hold significant translational potential. Further studies are needed to clarify FXR's tissue-specific functions and bidirectional mechanisms, and to develop highly selective modulators for precise liver disease prevention and treatment."

Journal • Review • Fibrosis • Hepatocellular Cancer • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Oncology • Solid Tumor • GPC3 • IL6 • NLRP3 • NOTCH1 • TLR4 • TNFA

Obeticholic Acid Rescues Male Reproductive Function in High-Fat Diet-Induced Metabolic Syndrome. (PubMed, Reprod Sci) - "These findings indicate that OCA is associated with improved male reproductive parameters in MetS through modulation of bile acid signaling, immune response, and microbiota. OCA may represent a potential therapeutic approach for MetS- associated male infertility."

Journal • Infertility • Metabolic Disorders • Sexual Disorders • CD4 • IFNG

Characteristics of Clinical Studies on Primary Biliary Cholangitis Registered in ClinicalTrials.gov: A Cross-Sectional Analysis (ACG 2026) - "Ursodeoxycholic acid (UDCA) remains first-line therapy, with obeticholic acid used for inadequate responders. Recent approvals of PPAR agonists seladelpar and elafibranor reflect a rapidly evolving therapeutic landscape... A total of 219 PBC studies were identified, representing 0.037% of 587,109 total CTG studies, with 63 (28.7%) ongoing. Of all PBC studies, 166 (75.8%) were interventional and 146 (66.7%) were pharmacological. Industry funding was significantly higher in PBC compared to all CTG (40.2% vs 28.1%; OR 1.73, 95% CI 1.32â2.26, p< 0.001), while NIH funding was significantly lower (3.7% vs 7.4%; OR 0.21, 95% CI 0.11â0.44, p< 0.001)."

Clinical • Cholestasis • Fibrosis • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

Comparative Real-World Likelihood of Complete Alkaline Phosphatase Normalization With Obeticholic Acid Versus Elafibranor in Primary Biliary Cholangitis (ACG 2026) - "Introduction: In patients with Primary Biliary Cholangitis (PBC) who respond inadequately to first-line Ursodeoxycholic Acid (UDCA), reducing Alkaline Phosphatase (ALP) is essential to slowing disease progression. Propensity matching generated two balanced cohorts of 444 patients each (N=888 total). The post-match cohorts were identical in age (mean 61.3 vs. 61.2 years) and female sex (92.8% vs."

Clinical • Real-world • Real-world evidence • Hepatology • Immunology • Primary Biliary Cholangitis

Primary Biliary Cholangitis After Roux-en-Y Gastric Bypass: A Case Highlighting Diagnostic and Therapeutic Challenges in the Setting of Malabsorption (ACG 2026) - "Obeticholic acid 5 mg daily was initiated in 2016, resulting in biochemical improvement and symptom resolution... Malabsorption following Roux-en-Y gastric bypass can result in reduced circulating levels of ursodeoxycholic acid (UDCA), leading to suboptimal therapeutic response and posing a significant challenge in the management of primary biliary cholangitis (PBC)...Figure: Figure 2. Trend of liver enzymes in U/L (AST, ALT and Alkaline phosphatase) over time (in years)."

Bariatric surgery • Clinical • Barrett Esophagus • Cholestasis • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

Elafibranor Is Effective in Real-World Settings in Patients With Primary Biliary Cholangitis Who Switched Treatment From Obeticholic Acid (ACG 2026) - P3 | "In total, 59 pts switched from OCA to ELA vs 305 ELA only; of these, 14 (Cohort 1) vs 108 (Cohort 2) met the full inclusion criteria. Median (IQR) ELA treatment duration was 171.5 (123.3, 298.3) vs 160.5 (90.0, 253.5) days. For Cohort 1, observed OCA treatment duration during the study period was 242.0 (205.3, 331.5) days and duration between OCA to ELA switch was 26.0 (17.8, 33.8) days."

Clinical • Real-world • Real-world evidence • Hepatology • Immunology • Primary Biliary Cholangitis

Epidemiology, Patient Characteristics, and Treatment Patterns Among Adults with Primary Biliary Cholangitis in the US (ACG 2026) - "In addition, 6,244/9,136 (72%) received monotherapy ursodeoxycholic acid (UDCA), 535/9,136 (6%) received second-line obeticholic acid (OCA), and 144/9,136 (2%) received off-label fibrates only. Of 113,080,636 adults in the US, 34,213 pts with PBC were identified, corresponding to a prevalence of 30.3 per 100,000. Among those pts, 9,136 were continuously enrolled in a health plan, with a mean (SD) age of 54.6 (13.87) years and median (Q1, Q3) follow-up time of 30 (20, 48) months. A large proportion of pts were female (82%) and had commercial insurance (51%)."

Clinical • Cardiovascular • Dyslipidemia • Fibrosis • Hepatocellular Cancer • Hepatology • Hypertension • Immunology • Metabolic Disorders • Musculoskeletal Pain • Primary Biliary Cholangitis • Pruritus • Solid Tumor

Racial Disparities in Primary Biliary Cholangitis: Increased Mortality and Intrahepatic Bile Duct Carcinoma Among Black Patients in a Propensity-Matched Cohort (ACG 2026) - "No significant differences were observed in HCC (OR 0.90, 95% CI 0.69â1.18), cirrhosis (OR 0.91, 95% CI 0.79â1.03), fibrosis (OR 1.08, 95% CI 0.93â1.25), HE (OR 0.81, 95% CI 0.64â1.04), ALP normalization (OR 0.97, 95% CI 0.84â1.11), UDCA use (OR 0.88, 95% CI 0.77â1.01), or obeticholic acid use (OR 0.80, 95% CI 0.56â1.13)... Before matching, Black patients had a higher burden of diabetes, chronic kidney disease, ischemic heart disease, and heart failure. After matching, baseline characteristics were balanced. Mean follow-up was 1,868 days in Black patients and 2,007 days in White patients."

Clinical • Biliary Cancer • Cardiovascular • Cholestasis • Chronic Kidney Disease • CNS Disorders • Congestive Heart Failure • Coronary Artery Disease • Diabetes • Fibrosis • Heart Failure • Hepatic Encephalopathy • Hepatocellular Cancer • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Metabolic Disorders • Nephrology • Oncology • Primary Biliary Cholangitis • Renal Disease • Solid Tumor

Repositioning Bezafibrate in the Second-Line Treatment of Primary Biliary Cholangitis: A Systematic Review and Meta-Analysis of Biochemical Response, Lipid Effects, and Clinical Outcomes (ACG 2026) - "Introduction: Up to 40% of patients with primary biliary cholangitis (PBC) respond inadequately to ursodeoxycholic acid (UDCA) and require second-line therapy. PubMed, EMBASE, and the Cochrane Central Register were searched from inception through December 2025 for studies of bezafibrate in adults with UDCA-refractory PBC. Outcomes were stratified a priori by comparator: bezafibrate+UDCA versus inactive control and versus obeticholic acid (OCA). ALP normalization proportions were pooled using a random-effects model (REML; logit transformation)."

Clinical data • Retrospective data • Review • Hepatology • Immunology • Primary Biliary Cholangitis

Comparative Efficacy and Safety of Emerging Second-Line Therapies for Primary Biliary Cholangitis: A Systematic Review and Network Meta-Analysis of Seladelpar, Elafibranor, and Obeticholic Acid (ACG 2026) - "A total of 9 randomized controlled trials comprising 2,184 patients with Primary Biliary Cholangitis were included. Overall, 1,962 (89.8%) were female, with a mean age ranging from 52â61 years and baseline alkaline phosphatase levels between 2.1â3.4 times the upper limit of normal. Seladelpar was evaluated in 812 patients, elafibranor in 604, obeticholic acid in 568, and placebo/standard therapy in 200 patients."

Retrospective data • Review • Cholestasis • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

ELEVATE-PBC: REAL-WORLD EVIDENCE IN UDCA NON-RESPONDERS PREVIOUSLY TREATED WITH OBETICHOLIC ACID OR FIBRATES (UEGW 2026) - No abstract available

Clinical • HEOR • Real-world • Real-world evidence • Primary Biliary Cholangitis

Study to Evaluate the Efficacy and Safety of K-808 (Pemafibrate) in Participants With Primary Biliary Cholangitis (PBC) With Inadequate Response to Ursodeoxycholic Acid (UDCA) and/or Obeticholic Acid (OCA) Treatment. (clinicaltrials.gov) - P2 | N=46 | Completed | Sponsor: Kowa Research Institute, Inc. | Active, not recruiting ➔ Completed

Trial completion • Hepatology • Immunology • Primary Biliary Cholangitis

Biliary atresia-related liver fibrosis. (PubMed, Front Cell Dev Biol) - "In therapeutics, we assess the enduring role of Kasai portoenterostomy (KPE), the limitations of current adjunctive therapies, and the evolving landscape of pharmacological interventions-including ileal bile acid transporter inhibitors (odevixibat), farnesoid X receptor agonists (obeticholic acid), eicosapentaenoic acid, and N-acetylcysteine-alongside ongoing clinical trials. We further highlight how single-cell and spatial transcriptomic technologies are revolutionizing our comprehension of cellular heterogeneity and intercellular crosstalk within the fibrotic niche, offering unprecedented opportunities for molecular subtyping and precision medicine. By bridging mechanistic insights with clinical translation, this review provides a conceptual framework to guide future research, improve diagnostic precision, and develop rationally targeted combination therapies for BA-associated liver fibrosis."

Journal • Review • Cholestasis • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Transplantation • GPC1 • MMP7 • TGFB1

Obeticholic acid as an index farnesoid X receptor scaffold in metabolic dysfunction-associated steatohepatitis: a testable model for efficacy-liability separation and biomarker interpretation. (PubMed, Front Pharmacol) - "The model is not a class-wide claim for all FXR agonists. It should be tested, and if necessary rejected, using matched FXR target engagement, paired human tissue and human multicellular systems."

Biomarker • Journal • Dermatology • Dyslipidemia • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Pruritus • ACOX1 • IL1B

Real-world treatment patterns and clinical outcomes of patients with primary biliary cholangitis in the United States. (PubMed, J Comp Eff Res) - "In the untreated, 1L, and 2L+ cohorts, 18.9%, 14.4% and 19.3% of patients developed ≥1 negative clinical outcome post-index (usually cirrhosis). Results of this US population-based study demonstrate a potential unmet need for early intervention and effective treatment options for patients with PBC, as one in three patients with PBC remain untreated years after diagnosis."

Clinical data • HEOR • Journal • Real-world evidence • Cholestasis • Fibrosis • Hepatology • Immunology • Primary Biliary Cholangitis

Treatment Goals for Primary Biliary Cholangitis, an Australian Perspective. (PubMed, J Gastroenterol Hepatol) - "Ursodeoxycholic acid (UDCA) is the mainstay of therapy and improves outcomes including transplant-free survival...Second-line treatments include selective peroxisome proliferator-associated receptor (PPAR) agonists, obeticholic acid (OCA; subject to precautions), and off-label use of fenofibrate...Normalization of ALP is an aspirational treatment target with increasing evidence for improved outcomes. Proactive and diligent monitoring of patients with PBC allows personalized selection and early initiation of effective and well-tolerated 2L therapies with potential for improved outcomes."

Journal • Review • Endocrine Disorders • Fatigue • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Osteoporosis • Primary Biliary Cholangitis • Rheumatology • Sjogren's Syndrome • Transplantation

Impact of Obeticholic Acid Therapy on Insulin Resistance and Metabolic Parameters in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). (PubMed, Int J Hepatol) - "Over 3 months, OCA combined with lifestyle modification improved liver enzymes, steatosis and fibrosis-related surrogate indices, and modestly reduced insulin resistance. Careful lipid monitoring is recommended, and longer term studies are required to clarify the overall metabolic and cardiovascular implications."

Journal • Cardiovascular • Coronary Artery Disease • Diabetes • Fibrosis • Heart Failure • Hepatitis C • Hepatology • Immunology • Infectious Disease • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease

A machine learning-derived aging-related gene signature for diagnosing HCV cirrhosis: Insights into immune microenvironment and therapeutic targets. (PubMed, Comput Biol Chem) - "We established a novel ARG-based diagnostic signature for HCV cirrhosis, highlighting its association with immune remodeling and pathogenic pathways. Notably, MMP7 is a promising target, providing insights for post-clearance disease management."

Gene Signature • Journal • Fibrosis • Gastroenterology • Hepatitis C • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis • Liver Failure • CTGF • GJA1 • MMP7

Regulation of Tph cell differentiation via farnesoid X receptor of dendritic cells in inflammatory bowel disease. (PubMed, Inflamm Res) - "Tph cell levels were elevated in inflamed intestinal tissues. FXR suppression in BMDCs was associated with activated PPAR-γ signaling; and with reduced DC maturation, IL-12 secretion, and Tph cell differentiation."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • CD4 • IL12A • ITGAX

Burden of primary biliary cholangitis on the Italian National Health Service: retrospective analysis from an administrative database. (PubMed, Glob Reg Health Technol Assess) - "During one-year follow-up of the prevalent cohort: 73.1% received ursodeoxycholic acid (UDCA); 3.0% obeticholic acid (OCA), and 3.4% off-label drugs; 19.9% were hospitalized, mainly for cirrhosis-related conditions; 61.2% were examined by a specialist. Among the 40 incident patients, 38 (95%) received UDCA as first-line therapy. The study described the real-world impact of PBC in Italy from the perspective of the SSN and highlighted the burden and therapeutic needs of patients treated with UDCA."

Journal • Retrospective data • Fibrosis • Hepatology • Immunology • Primary Biliary Cholangitis

AISF practice guidance on the treatment of primary biliary cholangitis: A 2026 update. (PubMed, Dig Liver Dis) - "Although ursodeoxycholic acid (UDCA) remains the cornerstone of first-line therapy and improves transplant-free survival, an important proportion of patients show an inadequate biochemical response, and many continue to experience substantial symptoms, particularly pruritus and fatigue, with a major impact on quality of life. In recent years, the therapeutic landscape of PBC has evolved following the withdrawal of obeticholic acid and the availability of selective PPAR agonists, including elafibranor and seladelpar...Therapeutic targets should be individualized according to age, disease stage, symptom burden, and risk of progression, distinguishing between "adequate" and "complete" biochemical response and supporting earlier treatment escalation in high-risk and symptomatic patients. This updated AISF guidance provides an evidence-based framework for PBC management in 2026 and beyond, reviewing therapeutic goals, response criteria, second-line..."

Journal • Review • Cholestasis • Dermatology • Fatigue • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Primary Biliary Cholangitis • Pruritus • Transplantation

Machine Learning Predicts Treatment Response and Prognostic Pathways From Whole-Blood Transcriptome in Primary Biliary Cholangitis. (PubMed, Liver Int) - "The ML-derived score links both prognostic and disease pathogenesis pathways and can be used in future studies to better understand the pathophysiology and management of PBC."

Biomarker • Journal • Fibrosis • Hepatology • Immunology • Inflammation • Liver Failure • Primary Biliary Cholangitis • Transplantation