Hepatology
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See the full rubric →Orchestrated cell death pathways in cholangiopathies.
Clinical takeawayNo clinical action yet: mechanistic review synthesizing cell death pathways. Current therapies bypass these mechanisms; human evidence for targeting them is pending.
What it foundCholangiopathies involve multiple regulated cell death pathways (apoptosis, necroptosis, pyroptosis, ferroptosis, autophagy-dependent) that intersect and form integrated programs (PANoptosis); sublethal activation of these pathways perpetuates cholangiocyte dysfunction independently of overt cell death.
ContextStandard therapies (ursodeoxycholic acid, PPAR agonists) improve biochemical markers but do not directly modify cell death mechanisms. This review synthesizes evidence that multiple intersecting death pathways drive progressive cholangiocyte loss and fibrosis, providing mechanistic rationale for targeted intervention research.
Emergingsuggested applicable standard· American Association for the Study of Liver Diseases, 'Primary Biliary Cholangitis: 2021 Practice Guidance', 2021
Decision at stakewhether to incorporate cell-death-pathway targeting into cholangiopathy management strategy
American Association for the Study of Liver Diseases, 'Primary Biliary Cholangitis: 2021 Practice Guidance', 2021 · reviewed 2026-07-21 ↗Treat with first-line ursodeoxycholic acid (UDCA) 13-15 mg/kg/d divided, and assess biochemical response at 12 months using Paris-II plus continuous risk scores (Globe, UK-PBC). Escalate to a second-line agent (obeticholic acid [contraindicated in cirrhosis with portal hypertension or prior decompensation], seladelpar, elafibranor, or a fibrate) when response is inadequate, guided by a Child-Pugh/portal-hypertension hard gate, and manage pruritus with a stepwise ladder (cholestyramine → rifampin → sertraline → naltrexone). Refer for transplant evaluation for decompensation, refractory pruritus, or rising bilirubin.
Guicciardi ME … Gautheron J · Gut · IF 24.6 · PubMed ↗