A SYSTEMATIC LITERATURE REVIEW OF PROGNOSTIC FACTORS AND EFFECT MODIFIERS IMPACTING TREATMENT OUTCOMES IN PRIMARY BILIARY CHOLANGITIS
Author(s)
Dilip Makhija, MS1, Marvin Rock, MPH, DrPH1, Chong H Kim, MPH, MS, PhD1, Caroline Burk, PhD1, Mirko von Hein, M.Sc.2, Ryan Thaliffdeen, BS, MS, PharmD1, Ankita Sood, PharmD3, Sunil Kumar, M.Pharm3, Barinder Singh, RPh3;
1Gilead Sciences, Inc., Foster City, CA, USA, 2Gilead Sciences, London, United Kingdom, 3Pharmacoevidence, Mohali, India
1Gilead Sciences, Inc., Foster City, CA, USA, 2Gilead Sciences, London, United Kingdom, 3Pharmacoevidence, Mohali, India
OBJECTIVES: Primary biliary cholangitis (PBC) is an autoimmune condition that leads to the progression of chronic cholestatic liver diseases. This systematic literature review (SLR) identifies prognostic factors (PFs) and effect modifiers (EMs) that influence disease progression and treatment response in PBC, to inform clinical decision-making, indirect treatment comparisons (ITCs), and economic modeling.
METHODS: Embase® and MEDLINE® were searched from database inception through August 2025. Citations were screened in parallel by a human reviewer and a GPT-4-based AI tool, with any discrepancies adjudicated by a human subject matter expert.
RESULTS: A total of 59 studies and two NICE technology appraisals (TAs) reporting PFs/EMs in PBC were identified. PFs/EMs clustered by domain included: demographics (age at diagnosis; male gender associated with poorer outcomes; family history); clinical/biochemical markers (baseline alkaline phosphatase/ALP, bilirubin, albumin, AST, gamma-glutamyl transferase, platelet count); immunologic/genetic factors (ANA, anti-mitochondrial and anti-gp210 antibodies; HLA-region variants); and comorbidity/lifestyle factors (smoking, elevated BMI, autoimmune disease history, and deficiencies in vitamin D and calcium). Younger age, male sex, and anti-gp210 positivity predicted poorer biochemical response to first-line ursodeoxycholic acid (UDCA). UDCA non-responders had >4.5-fold increased risk of hepatocellular carcinoma. Male gender, inadequate UDCA response, and diabetes were linked to significantly ~2-fold higher risk of progression to cirrhosis. Advanced age, serum bilirubin, ALP, albumin, and AST/ALT were strong predictors of transplant-free survival.
CONCLUSIONS: This SLR highlights that multiple patient, disease, and clinical factors influence outcomes in PBC. Collectively, these findings reinforce the importance of ALP reduction and normalization to reduce risk of PBC disease progression, and support future studies including ITCs and payer-relevant economic models and strengthen the validity of comparative effectiveness research in PBC.
METHODS: Embase® and MEDLINE® were searched from database inception through August 2025. Citations were screened in parallel by a human reviewer and a GPT-4-based AI tool, with any discrepancies adjudicated by a human subject matter expert.
RESULTS: A total of 59 studies and two NICE technology appraisals (TAs) reporting PFs/EMs in PBC were identified. PFs/EMs clustered by domain included: demographics (age at diagnosis; male gender associated with poorer outcomes; family history); clinical/biochemical markers (baseline alkaline phosphatase/ALP, bilirubin, albumin, AST, gamma-glutamyl transferase, platelet count); immunologic/genetic factors (ANA, anti-mitochondrial and anti-gp210 antibodies; HLA-region variants); and comorbidity/lifestyle factors (smoking, elevated BMI, autoimmune disease history, and deficiencies in vitamin D and calcium). Younger age, male sex, and anti-gp210 positivity predicted poorer biochemical response to first-line ursodeoxycholic acid (UDCA). UDCA non-responders had >4.5-fold increased risk of hepatocellular carcinoma. Male gender, inadequate UDCA response, and diabetes were linked to significantly ~2-fold higher risk of progression to cirrhosis. Advanced age, serum bilirubin, ALP, albumin, and AST/ALT were strong predictors of transplant-free survival.
CONCLUSIONS: This SLR highlights that multiple patient, disease, and clinical factors influence outcomes in PBC. Collectively, these findings reinforce the importance of ALP reduction and normalization to reduce risk of PBC disease progression, and support future studies including ITCs and payer-relevant economic models and strengthen the validity of comparative effectiveness research in PBC.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
EPH124
Topic
Epidemiology & Public Health
Disease
SDC: Rare & Orphan Diseases, SDC: Systemic Disorders/Conditions (Anesthesia, Auto-Immune Disorders (n.e.c.), Hematological Disorders (non-oncologic), Pain)