What is the Barcelona formula for evaluating response to treatment in Primary Biliary Cholangitis (PBC)?

Barcelona Criteria for Evaluating Response to Treatment in Primary Biliary Cholangitis

The Barcelona criteria defines treatment response in Primary Biliary Cholangitis (PBC) as a decrease of 40% or normalization of serum alkaline phosphatase (ALP) after one year of ursodeoxycholic acid (UDCA) treatment. 1

Understanding the Barcelona Criteria

The Barcelona criteria is one of several qualitative criteria used to assess biochemical response to UDCA therapy in PBC patients. It focuses specifically on alkaline phosphatase levels as the key marker of treatment response.

Key Features:

• Definition: Decrease of ≥40% in ALP level OR normalization of ALP after 12 months of UDCA therapy
• Assessment timing: Evaluated after 1 year of treatment
• Clinical significance: Predicts long-term outcomes including liver transplant-free survival

Comparison with Other Response Criteria

The Barcelona criteria is one of several validated response criteria used in PBC. Others include:

Criteria	Definition	Assessment Time
Barcelona	≥40% decrease or normalization of ALP	12 months
Paris I	ALP ≤3× ULN, AST ≤2× ULN, normal bilirubin	12 months
Paris II	ALP ≤1.5× ULN, AST ≤1.5× ULN, normal bilirubin	12 months
Toronto	ALP <1.67× ULN	24 months
Rotterdam	Normalization of abnormal bilirubin and/or albumin	12 months

Clinical Application

The Barcelona criteria should be used alongside other tools for comprehensive risk stratification:

1. Baseline assessment:

   • Distinguish early from advanced disease using:
     • Liver stiffness measurement (LSM) by transient elastography (<10 kPa vs >10 kPa)
     • Serum bilirubin and albumin (both normal vs. at least one abnormal)

2. On-treatment assessment (after 12 months of UDCA):

   • Apply Barcelona criteria to evaluate biochemical response
   • Consider using quantitative risk scores (GLOBE and UK-PBC) for more precise risk stratification
   • Monitor liver stiffness by transient elastography

Importance in Treatment Decisions

Identifying non-responders using the Barcelona criteria has significant implications:

• Non-responders have higher risk of disease progression and adverse outcomes
• Early identification allows timely initiation of second-line therapies
• Recent research suggests that earlier assessment at 6 months may identify most non-responders, with ALP >1.9× ULN at 6 months having 89% negative predictive value for response at 12 months 2

Pitfalls and Limitations

• The Barcelona criteria is simpler but may be less comprehensive than newer criteria like Paris I/II
• It does not incorporate other important prognostic markers like bilirubin
• Quantitative risk scores (GLOBE and UK-PBC) may provide more precise risk stratification than qualitative criteria alone 1
• Isolated use of Barcelona criteria without considering other factors may miss patients who would benefit from additional therapy

Practical Recommendations

1. Measure baseline ALP before starting UDCA therapy (13-15 mg/kg/day)
2. Reassess ALP after 12 months of compliant UDCA therapy
3. Calculate percent reduction from baseline and determine if normalized
4. If criteria not met (reduction <40% and not normalized), consider patient as a non-responder
5. For non-responders, consider second-line therapies (obeticholic acid, bezafibrate) in addition to continued UDCA 3, 4
6. Continue monitoring with regular liver biochemistry and non-invasive fibrosis assessment

The Barcelona criteria remains an important tool in the management algorithm for PBC, helping clinicians identify patients who may need intensification of therapy beyond UDCA alone to improve long-term outcomes.