Three second-line therapies for primary biliary cholangitis hold conditional approval. None has converted that into full approval, and this consensus explains why: the field relies on liver biochemistry and non-invasive fibrosis measures as stand-ins for clinical outcomes, and regulators do not accept them as validated efficacy endpoints. Real-world evidence is used inconsistently, and patient-reported outcomes are not standardised.
EASL and AASLD convened 62 panellists across three working groups - clinicians, methodologists, regulators, industry and patient representatives - and ran a modified Delphi process with two voting rounds, with response rates of 88% and 60%. The output is 16 statements and 42 recommendations across those three domains, framed explicitly as a pathway aligned to regulatory expectations rather than as a clinical guideline.
The honest description of what this is: a framework for how future trials should be designed and analysed, not a change to how a patient is treated tomorrow. Conditional approval status is unchanged, and no new therapy has been approved or restricted here.
What it is worth to a clinician is context for a conversation patients do have. When someone asks why a drug they are taking is 'not fully approved', the answer is not that it does not work but that the endpoint used to show it works has not been validated against outcomes - and the profession has now agreed what validating it would take. It also flags that patient-reported outcomes, particularly fatigue and itch, are being taken seriously as endpoints rather than as secondary observations.
- Conditional approval means the outcome evidence is incomplete, not that the drug is unproven to work
- Alkaline phosphatase response remains the practical monitoring tool regardless of its regulatory status
- Record itch and fatigue systematically - they are becoming trial endpoints and they matter to patients
- Do not describe this consensus as a treatment guideline; it is a research and regulatory framework
- Second-line therapy availability in India follows CDSCO approvals, which this document does not address
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