Comparison of studies evaluating the impact of coexisting MASLD on disease severity and progression in PBC.
| Feature | Híndi et al., 2013 [34] | Minuk et al., 2018 [17] | Iluz-Freundlich et al., 2021 [32] | Hernández-Pérez et al., 2024 [24] | Drazilova et al., 2026 [22] | Del Barrio et al., 2026 [25] | Ren et al., 2025 [33] |
|---|---|---|---|---|---|---|---|
| Study design | Retrospective biopsy review | Retrospective cohort | Retrospective cohort | Retrospective two-center cohort | Cross-sectional | Retrospective multicenter cohort (ColHai registry) | Retrospective cohort |
| Sample size | 49 AMA-positive PBC patients | 168 PBC alone vs. 68 PBC/MASLD | 136 MASLD alone vs. 68 MASLD/PBC | 129 biopsy-proven PBC patients | 152 PBC patients | 469 PBC patients (158 with SLD, 124 with MASLD) | 363 PBC patients (87 with concurrent MASLD) |
| Comparison groups | PBC with MASH vs. PBC without MASH | PBC alone vs. PBC/MASLD | MASLD alone vs. MASLD/PBC | PBC with MASLD vs. PBC without MASLD | PBC patients stratified by MASLD and MetS; age/sex-matched controls used for prevalence comparison | PBC with SLD vs. PBC without SLD | PBC alone vs. PBC/MASLD |
| MASLD definition | Histologic MASH in AMA-positive PBC biopsies | Biochemical criteria/noninvasive scores | Biochemical criteria/noninvasive scores | Histology (biopsy-proven). MASLD defined as steatosis > 5% + ≥ 1 metabolic risk factor | Noninvasive imaging (TE/CAP) | Imaging and/or clinical criteria (78.5% met MASLD criteria) | Clinical criteria per 2023 AASLD guidelines |
| Outcome measures | Histological severity: ductal biliary damage, inflammation | LFTs (ALP, GGT), Fib-4, APRI | LFTs, Fib-4, APRI, INR, albumin | Validated PBC scores (Paris II, Toronto, APRI, Globe, UK PBC) at 5, 10, 15 years; liver-related mortality and transplantation | TE, biochemical response to UDCA | UDCA response at 1 year (Paris II, GLOBE, UK-PBC, deep response, complete normalization); liver-related events | Biochemical response (Paris criteria); APRI, Fib-4; GLOBE score |
| Key findings | MASH is associated with more severe ductal damage and fibrosis | PBC-alone had higher baseline activity (ALP, GGT) and severity (Fib-4); progression appeared worse in PBC-alone but not statistically significant | MASLD/PBC group had lower and less deterioration of Fib-4 vs. MASLD alone at follow-up | Coexisting MASLD associated with significantly worse treatment response and higher liver-related mortality/transplantation; steatosis/dyslipidemia/advanced fibrosis independently associated with worse outcomes | MetS (not MASLD) independently associated with advanced fibrosis (OR 4.561); MASLD prevalence similar to controls (42.3% vs. 41.9%); neither MASLD nor MetS affected UDCA response | SLD not associated with adverse UDCA response at 1 year by any criteria or liver-related events | Biochemical response rates similar; PBC/MASLD had lower APRI and Fib-4 after 1-year UDCA; and better predicted transplant-free survival |
| MASLD vs. MetS distinction | Overweight associated with advanced fibrosis, but not formally separated | Not addressed | Not addressed | Steatosis (not MASH) independently associated with worse outcomes after adjusting for metabolic comorbidities | Key finding: MetS, not MASLD, drives fibrosis; each additional MetS criterion increases risk 1.9-fold | 78.5% of SLD patients met MASLD criteria; metabolic comorbidities noted but not independently analyzed as driver | Not formally separated |
| Principal limitations | Small sample, cross-sectional, no longitudinal follow-up | Retrospective, single-center, disease activity assessed using biochemical markers, no histology | Retrospective, no histology | Retrospective, modest sample size (n = 129), 36% of MASLD had MASH, older age in the PBC/MASLD group | Cross-sectional, no histology, cannot assess longitudinal progression | Retrospective, no histologic confirmation of SLD in most patients | Retrospective, no histology, MASLD defined clinically, single-center |
ALP: alkaline phosphatase; AMA: anti-mitochondrial antibodies; APRI: AST-to-platelet ratio index; CAP: controlled attenuation parameter; Fib-4: Fibrosis-4 index; GGT: gamma-glutamyl transferase; INR: international normalized ratio; LFTs: liver function tests; MASH: metabolic dysfunction-associated steatohepatitis; MASLD: metabolic dysfunction-associated steatotic liver disease; MetS: metabolic syndrome; OR: odds ratio; PBC: primary biliary cholangitis; SLD: steatotic liver disease, TE: transient elastography; UDCA: ursodeoxycholic acid.